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1.
J Hum Genet ; 65(4): 411-420, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31959871

RESUMO

Genome-wide association studies (GWASs) have identified many genetic variations associated with type 2 diabetes mellitus (T2DM) in Asians, but understanding the functional genetic variants that influence traits is often a complex process. In this study, fine mapping and other analytical strategies were performed to investigate the effects of G protein signaling modulator 1 (GPSM1) on insulin resistance in skeletal muscle. A total of 128 single-nucleotide polymorphisms (SNPs) within GPSM1 were analysed in 21,897 T2DM cases and 32,710 healthy controls from seven GWASs. The SNP rs28539249 in intron 9 of GPSM1 showed a nominally significant association with T2DM in Asians (OR = 1.07, 95% CI = 1.04-1.10, P < 10-4). The GPSM1 mRNA was increased in skeletal muscle and correlated with T2DM traits across obese mice model. An eQTL for the cis-acting regulation of GPSM1 expression in human skeletal muscle was identified for rs28539249, and the increased GPSM1 expression related with T2DM traits within GEO datasets. Another independent Asian cohort showed that rs28539249 is associated with the skeletal muscle expression of CACFD1, GTF3C5, SARDH, and FAM163B genes, which are functionally enriched for endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) pathways. Moreover, rs28539249 locus was predicted to disrupt regulatory regions in human skeletal muscle with enriched epigenetic marks and binding affinity for CTCF. Supershift EMSA assays followed luciferase assays demonstrated the CTCF specifically binding to rs28539249-C allele leading to decreased transcriptional activity. Thus, the post-GWAS annotation confirmed the Asian-specific association of genetic variant in GPSM1 with T2DM, suggesting a role for the variant in the regulation in skeletal muscle.

3.
Hand (N Y) ; 15(1): 103-110, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30003806

RESUMO

Background: A radial incision with radial plate fixation for distal radius fracture has historically been avoided due to its risk to the superficial branch of the radial nerve (SBRN). With careful technique, it is possible to avoid injury to the SBRN, thereby minimizing the soft tissue injury associated with other approaches. We compare subjective and objective functional outcomes of radial plate fixation surgeries that we performed with those of dorsal and volar plate fixation in current literature. Methods: Patients at a single center who underwent radial plate fixation for an AO type A or AO type B distal radius fracture between December 2006 and December 2014 were enrolled in the study. Postoperative grip strength and 3-digit pinch strength were measured systematically in the injured and uninjured wrists. Patients also completed a Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire to assess subjective outcomes. Results: Thirty-six patients met our inclusion criteria and had available medical records. Postoperative grip strength in the injured wrist was significantly lowered-68% compared with the uninjured wrist. After subgroup analysis of dominant and nondominant wrist injuries, there was no significant difference in grip strength between injured and uninjured wrists. There was no significant decrease in postoperative 3-digit pinch strength in the injured wrist-89% compared with the uninjured wrist. The mean QuickDASH score for our study participants was 20.9. Conclusions: Radial plate fixation is an effective approach for distal radius fractures. Objective and subjective outcomes are noninferior to those of a dorsal or volar approach.

4.
J Mol Biol ; 432(2): 305-323, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31628947

RESUMO

Von Willebrand factor (VWF), an exceptionally large multimeric plasma glycoprotein, functions to initiate coagulation by agglutinating platelets in the blood stream to sites of vascular injury. This primary hemostatic function is perturbed in type 2 dysfunctional subtypes of von Willebrand disease (VWD) by mutations that alter the structure and function of the platelet GPIbα adhesive VWF A1 domains. The resulting amino acid substitutions cause local disorder and misfold the native structure of the isolated platelet GPIbα-adhesive A1 domain of VWF in both gain-of-function (type 2B) and loss-of-function (type 2M) phenotypes. These structural effects have not been explicitly observed in A1 domains of VWF multimers native to blood plasma. New mass spectrometry strategies are applied to resolve the structural effects of 2B and 2M mutations in VWF to verify the presence of A1 domain structural disorder in multimeric VWF harboring type 2 VWD mutations. Limited trypsinolysis mass spectrometry (LTMS) and hydrogen-deuterium exchange mass spectrometry (HXMS) are applied to wild-type and VWD variants of the single A1, A2, and A3 domains, an A1A2A3 tridomain fragment of VWF, plasmin-cleaved dimers of VWF, multimeric recombinant VWF, and normal VWF plasma concentrates. Comparatively, these methods show that mutations known to misfold the isolated A1 domain increase the rate of trypsinolysis and the extent of hydrogen-deuterium exchange in local secondary structures of A1 within multimeric VWF. VWD mutation effects are localized to the A1 domain without appreciably affecting the structure and dynamics of other VWF domains. The intrinsic dynamics of A1 observed in recombinant fragments of VWF are conserved in plasma-derived VWF. These studies reveal that structural disorder does occur in VWD variants of the A1 domain within multimeric VWF and provides strong support for VWF misfolding as a result of some, but not all, type 2 VWD variants.

5.
Eur J Clin Nutr ; 74(1): 149-157, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31142827

RESUMO

BACKGROUND/OBJECTIVES: Intrauterine growth restriction (IUGR) and low-birth-weight (LBW) are determinant factors in the development of metabolic diseases in children and adolescents. To estimate the magnitude of the association between LBW and IUGR with stunting or obesity among adolescents of two indigenous regions of the southern State of Chiapas, Mexico. SUBJECTS/METHODS: We assessed a random sample of 303 adolescents selected from a birth cohort study (2003) conducted in three hospitals serving urban and rural communities of Tzotzil-Tzeltal and Selva regions of Chiapas, Mexico. Sociodemographic and anthropometric data from a sample of adolescents were correlated with their anthropometric data at birth (weight, length for age). Logistic regression models were fitted to estimate odds ratios (OR) with 95% confidence intervals to measure the magnitude of the association among the variables of interest. Models were adjusted for potential confounders. RESULTS: In all, 12% of the sample had LBW and 28.8% IUGR. In total, 29% of adolescents were overweight/obese and 21% were stunted. We found a statistically significant association between IUGR and a lower risk of being overweight/obese. A higher probability for stunting was observed for LBW and IUGR. CONCLUSIONS: Stunting and overweight/obesity prevalence in this population of adolescents was high and was associated with IUGR.

6.
Ann Hum Genet ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799723

RESUMO

The polymorphisms rs3758391 and rs1800470 located in SIRT1 and TGF-ß1 have been associated with type 2 diabetes in different populations but its functional effect is not clear. In this study, we evaluated their effect on the expression of SIRT1 and TGF-ß1 in peripheral blood as well as their participation in the formation of DNA-protein complexes in a pancreas-derived cell line. It has been described that SIRT1 and TGF-ß1 participate in cell growth and regulation of production and secretion of insulin in the pancreas. Anthropometric and biochemical profiles of 127 adults were measured. Genotypes for rs3758391 and rs1800470 were determined using TaqMan assays. Expression analysis of SIRT1 and TGF-ß1 were performed using real-time PCR. Gene expression of these genes increased 1.8 ± 0.6- and 1.3 ± 0.6-fold in patients carrying the TT genotype of rs3758391 and rs1800470 when compared to carriers of the CC genotype. Then, we tested whether these single-nucleotide polymorphisms (SNPs) (and rs932658, which is in linkage disequilibrium with rs3758391) are located in regulatory DNA-protein binding sites by electrophoretic mobility shift assays using nuclear extract from the pancreas-derived cell line BxPC-3. The electrophoretic mobility shift assay showed no binding of nuclear proteins to DNA. In conclusion, the genotypes of rs3758391 and rs1800470 are associated with modifications in the expression of the genes SIRT1 and TGF-ß1, respectively, but none of the tested SNPs are located in regulatory DNA-protein binding sites.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31841602

RESUMO

OBJECTIVE AND DESIGN: We investigated whether deleterious mutations in MC4R contribute to obesity in Mexican children and adults. RESULTS: We provide evidence that the MC4R p.Ile269Asn (rs79783591) mutation may have arisen in modern human populations from a founder event in native Mexicans. The MC4R Isoleucine 269 is perfectly conserved across 184 species, which suggests a critical role for the amino acid in MC4R activity. Four in silico tools (SIFT, PolyPhen-2, CADD, MutPred2) predicted a deleterious impact of the p.Ile269Asn substitution on MC4R function. The MC4R p.Ile269Asn mutation was associated with childhood (Ncontrols=952, Ncases=661, odds ratio (OR)=3.06, 95% confidence interval (95%CI) [1.94-4.85]) and adult obesity (Ncontrols=1,445, Ncases=2,487, OR=2.58, 95%CI [1.52-4.39]). The frequency of the MC4R p.Ile269Asn mutation ranged from 0.52-0.59% and 1.53-1.59% in children and adults with normal weight and obesity, respectively. The MC4R p.Ile269Asn mutation co-segregated perfectly with obesity in five multigenerational Mexican pedigrees. While adults with obesity carrying the p.Ile269Asn mutation had higher BMI values than non-carriers, this trend was not observed in children. The MC4R p.Ile269Asn mutation accounted for a population attributable risk of 1.28% and 0.68% for childhood and adult obesity, respectively, in the Mexican population. CONCLUSION: The MC4R p.Ile269Asn mutation may have emerged as a founder mutation in native Mexicans and is associated with childhood and adult obesity in the modern Mexican population.

9.
Int J Mol Sci ; 20(21)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31652968

RESUMO

Gluconacetobacter diazotrophicus PAL5 (GDI) is an endophytic bacterium with potential biotechnological applications in industry and agronomy. The recent description of its complete genome and its principal metabolic enzymes suggests that glucose metabolism is accomplished through the pentose phosphate pathway (PPP); however, the enzymes participating in this pathway have not yet been characterized in detail. The objective of the present work was to clone, purify, and biochemically and physicochemically characterize glucose-6-phosphate dehydrogenase (G6PD) from GDI. The gene was cloned and expressed as a tagged protein in E. coli to be purified by affinity chromatography. The native state of the G6PD protein in the solution was found to be a tetramer with optimal activity at pH 8.8 and a temperature between 37 and 50 °C. The apparent Km values for G6P and nicotinamide adenine dinucleotide phosphate (NADP+) were 63 and 7.2 µM, respectively. Finally, from the amino acid sequence a three-dimensional (3D) model was obtained, which allowed the arrangement of the amino acids involved in the catalytic activity, which are conserved (RIDHYLGKE, GxGGDLT, and EKPxG) with those of other species, to be identified. This characterization of the enzyme could help to identify new environmental conditions for the knowledge of the plant-microorganism interactions and a better use of GDI in new technological applications.

10.
Medicine (Baltimore) ; 98(39): e17298, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574854

RESUMO

Recently, studies have shown significant association between the rs2000999 polymorphism in the haptoglobin-encoding gene (HP) and low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, which are important risk factors for cardiovascular diseases. However, the association of rs2000999 with serum lipids in Latin American diabetic populations is still uncharacterized. Here, we analyzed the association of rs2000999 with TC, high-density lipoprotein cholesterol (HDL-C), and LDL-C levels in 546 Mexican adults with type 2 diabetes (T2D) and in 654 controls without T2D. In this observational case-control study we included adults from 4 centers of the Mexican Social Security Institute in Mexico City recruited from 2012 to 2015. TC, HDL-C, LDL-C, triglycerides (TG), and glucose levels were measured by an enzymatic colorimetric method. The variant rs2000999 was genotyped using TaqMan real time polymerase chain reaction. The percentage of Native-American ancestry showed a negative association with the rs2000999 A allele. In contrast, the rs2000999 A allele had a strong positive association with European ancestry, and to a lesser extent, with African ancestry. Linear regression was used to estimate the association between the variant rs2000999 and lipid concentrations, using different genetic models. Under codominant and recessive models, rs2000999 was significantly associated with TC and LDL-C levels in the T2D group and in controls without T2D. In addition, the group with T2D showed a significant association between the variant and HDL-C levels. In summary, the rs2000999 A allele in Mexican population is positively associated with the percentage of European and negatively associated with Native American ancestry. Carriers of the A allele have increased levels of TC and LDL-C, independently of T2D diagnosis, and also increased concentrations of HDL-C in the T2D sample.


Assuntos
Doenças Cardiovasculares , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Diabetes Mellitus Tipo 2 , Haptoglobinas , Adulto , Biomarcadores/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Haptoglobinas/análise , Haptoglobinas/genética , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
12.
Front Microbiol ; 10: 1685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417507

RESUMO

Enterotoxigenic Escherichia coli produces a myriad of adhesive structures collectively named colonization factors (CFs). CS3 is a CF, which is assembled into fine wiry fibrillae encoded by the cstA-H gene cluster. In this work we evaluated the influence of environmental cues such as temperature, osmolarity, pH, and carbon source on the expression of CS3 genes. The transcription of cstH major pilin gene was stimulated by growth of the bacteria in colonization factor broth at 37°C; the presence of glycerol enhanced cstH transcription, while glucose at high concentration, high osmolarity, and the depletion of divalent cations such as calcium and magnesium repressed cstH expression. In addition, we studied the role of H-NS, CpxRA, and CRP global regulators in CS3 gene expression. H-NS and CpxRA acted as repressors and CRP as an activator of cstH expression. Under high osmolarity, H-NS, and CpxRA were required for cstH repression. CS3 was required for both, bacterial adherence to epithelial cells and biofilm formation. Our data strengthens the existence of a multi-factorial regulatory network that controls transcription of CS3 genes in which global regulators, under the influence of environmental signals, control the production of this important intestinal colonization factor.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31380298

RESUMO

Klebsiella pneumoniae successfully colonizes host tissues by recognizing and interacting with cholesterol present on membrane-associated lipid rafts. In this study, we evaluated the role of cholesterol in the expression of capsule polysaccharide genes of K. pneumoniae and its implication in resistance to phagocytosis. Our data revealed that exogenous cholesterol added to K. pneumoniae increases macrophage-mediated phagocytosis. To explain this event, the expression of capsular galF, wzi, and manC genes was determined in the presence of cholesterol. Down-regulation of these capsular genes occurred leading to increased susceptibility to phagocytosis by macrophages. In contrast, depletion of cholesterol from macrophage membranes led to enhanced expression of galF, wzi, and manC genes and to capsule production resulting in resistance to macrophage-mediated phagocytosis. Cholesterol-mediated repression of capsular genes was dependent on the RcsA and H-NS global regulators. Finally, cholesterol also down-regulated the expression of genes responsible for LPS core oligosaccharides production and OMPs. Our results suggest that cholesterol plays an important role for the host by reducing the anti-phagocytic properties of the K. pneumoniae capsule facilitating bacterial engulfment by macrophages during the bacteria-eukaryotic cell interaction mediated by lipid rafts.

14.
Cir Cir ; 87(4): 377-384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264987

RESUMO

Objective: To describe the clinical presentation of the facial nerve schwannomas according to the anatomical site of origin. Method: A retrospective study in which the clinical presentation, diagnostic protocol and treatment of facial nerve tumors in adults was evaluated. Results: We found 6 cases, 4 cases of tympanic-mastoid location at the spectrum of its possible clinical presentation: from symptomatic cases with facial paralysis, to an asymptomatic case in the tympanic portion found as intraoperative finding; and also found two cases located at the parotid gland, one with complete facial paralysis and one without facial palsy. Conclusions: For the diagnosis of intratemporal and parotid schwannomas of the facial nerve, a high clinical suspicion is required given its heterogeneous presentation; its clinical course depends on the segment of origin and expansion: more frequently asymptomatic at the tympanic horizontal portion and symptomatic at the mastoid vertical portion. These tumors must be assessed with imaging studies, incisional biopsy is not recommended. The treatment is surgical resection in symptomatic patients with facial paralysis greater than grade III of House-Brackmann, with immediate reconstruction of the nerve.


Assuntos
Neoplasias dos Nervos Cranianos/complicações , Doenças do Nervo Facial/complicações , Processo Mastoide/inervação , Neurilemoma/complicações , Neoplasias Parotídeas/complicações , Membrana Timpânica/inervação , Adulto , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/cirurgia , Doenças do Nervo Facial/patologia , Doenças do Nervo Facial/cirurgia , Paralisia Facial/etiologia , Paralisia Facial/cirurgia , Feminino , Perda Auditiva Condutiva/etiologia , Humanos , Masculino , Neurilemoma/patologia , Neurilemoma/cirurgia , Glândula Parótida/inervação , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia , Estudos Retrospectivos , Zumbido/etiologia , Adulto Jovem
15.
Mol Med Rep ; 20(3): 2189-2198, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257515

RESUMO

Recent studies demonstrated that the expression of coxsackievirus and adenovirus receptor (CAR) is implicated in the pathophysiology of myocarditis. The aim of the present study was to assess the association between active and borderline myocarditis and CAR expression in endomyocardial tissues, and analyze the association between CAR expression and treatment response. An analytic, cross­sectional, retrospective study was performed in 26 patients with myocarditis and 10 control subjects without heart disease. Myocardial biopsies were obtained and CAR transcription was measured by reverse transcription­quantitative polymerase chain reaction analysis. The association between CAR mRNA levels and the response to immunosuppressive or conventional therapy (treatment responders, n=17; non­responders, n=9) or with the type of histological myocarditis (active myocarditis, n=16; borderline myocarditis, n=10) was analyzed. CAR transcription levels were significantly lower (P=0.012) in patients with myocarditis compared with controls, and a significant decrease was observed (P=0.023) in CAR mRNA levels among patients with borderline myocarditis compared with the no myocarditis group. Patients responding to therapy exhibited higher CAR mRNA levels (P=0.036) compared with patients not responding to treatment, as evaluated based on clinical and echocardiographic criteria (immunosuppressive therapy, n=8; conventional therapy, n=1). Myocarditis in non­responders was associated with fewer clinical manifestations and lower CAR mRNA levels. A significant difference was only found regarding the use of oral steroids in patients with active myocarditis who responded to treatment (P=0.02), with no difference in borderline myocarditis. In conclusion, the transcriptional level of CAR is low in the endomyocardial tissue of patients with myocarditis, and it is lower in borderline myocarditis and in non­responder patients. These findings may enable early identification of patients who may benefit from treatment and timely determination of prognosis.


Assuntos
Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/genética , Miocardite/genética , Miocárdio/patologia , Adulto , Estudos Transversais , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Miocárdio/metabolismo , RNA Mensageiro/genética , Adulto Jovem
17.
Front Neurol ; 10: 542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191436

RESUMO

Introduction: Orofacial pain and dysfunction include a broad range of disturbances among which pain and insomnia are some of the most common complaints. Sleep strengthens physiological and psychological resilience and is an absolute requirement for health. Insomnia is a common symptom or sleep disorder, yet data on its prevalence is sparse. Here we extracted data from the insomnia severity index which was part of the web-based interdisciplinary symptom evaluation (WISE) tool given to a large sample of patients seeking care at an orofacial pain unit for analyzing insomnia prevalence in this clinical population. Material and methods: Anonymized data were available from 952 patients who consulted the Orofacial Pain Unit at the Center of Dental Medicine, University of Zurich, Zurich, Switzerland between January 2017 and December 2018. Prevalence data for insomnia stratified by gender and 10 age groups (decades) were calculated. The distribution of four insomnia severity grades was determined, also stratified by age and gender. Results: 952 patients (290 men: 30.5%) with a mean age of 44.8 ± 17.4 years completed a WISE. Three hundred and fifty-two (37.0%) patients with a mean age of 45.8 ± 16.7 years positively responded to a screening question for insomnia and/or hypersomnia. Insomnia was severe in women from the 2nd to 8th decade, ranging from 4.3% (3rd decade) to 14.5% (6th decade), and moderately severe from the 2nd to 9th decade, ranging from 18.8% (6th decade) to 27.8% (2nd decade). In men, severe insomnia was present from the 3rd to 7th decade, ranging from 2.3% (7th decade) to 4.4% (4th decade) and moderately severe insomnia from the 3rd to 7th decade, ranging from 4.6% (7th decade) to 12.2% (5th decade). Conclusions: This is the first study reporting on insomnia in a large sample of patients seeking care at an orofacial pain unit. One in three patients reported some form of sleep disturbances, which for almost half of them was moderate to severe insomnia. The gender ratio was almost equal throughout adulthood, yet younger and older women were more frequently affected and experienced higher insomnia severity than men.

18.
Rev Alerg Mex ; 66(2): 257-262, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31200424

RESUMO

BACKGROUND: Food protein-induced enterocolitis syndrome or FPIES is a rare, not-IgE-mediated food allergy. The predominant feature is vomit from one to four hours after consuming the causal food. CLINICAL CASE: An 8-month-old boy, with no family history of allergy, with a personal pathological history of allergy to cow's milk protein. At 7 months of age, he had acute gastroenteritis with mixed shock and, at 8 months of age, he had acute gastroenteritis and moderate dehydration. In both episodes, he had eaten rice before the symptoms started. When infectious etiology and other causes of vomit and dehydration were ruled out, the diagnosis of FPIES, which is secondary to rice protein, was made and confirmed with a patch test. CONCLUSION: FPIES should be considered in the differential diagnosis of recurrent gastroenteritis, especially in severe cases without an identified infectious cause.


Assuntos
Proteínas na Dieta/efeitos adversos , Proteínas na Dieta/imunologia , Enterocolite/etiologia , Hipersensibilidade Alimentar/complicações , Humanos , Lactente , Masculino , Síndrome
19.
Mol Biol Cell ; 30(16): 1920-1929, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-31067148

RESUMO

Hemodynamic forces activate the Von Willebrand factor (VWF) and facilitate its cleavage by a disintegrin and metalloprotease with thrombospondin motifs-13 (ADAMTS13), reducing the adhesive activity of VWF. Biochemical assays have mapped the binding sites on both molecules. However, these assays require incubation of two molecules for a period beyond the time allowed in flowing blood. We used a single-molecule technique to examine these rapid, transient, and mechanically modulated molecular interactions in short times under forces to mimic what happens in circulation. Wild-type ADAMTS13 and two truncation variants that either lacked the C-terminal thrombospondin motif-7 to the CUB domain (MP-TSP6) or contained only the two CUB domains (CUB) were characterized for interactions with coiled VWF, flow-elongated VWF, and a VWF A1A2A3 tridomain. These interactions exhibited distinctive patterns of calcium dependency, binding affinity, and force-regulated lifetime. The results suggest that 1) ADAMTS13 binds coiled VWF primarily through CUB in a calcium-dependent manner via a site(s) outside A1A2A3, 2) ADAMTS13 binds flow-extended VWF predominantly through MP-TSP6 via a site(s) different from the one(s) at A1A2A3; and 3) ADAMTS13 binds A1A2A3 through MP-TSP6 in a Ca2+-dependent manner to autoinhibit another Ca2+-independent binding site on CUB. These data reveal that multiple sites on both molecules are involved in mechanically modulated VWF-ADAMTS13 interaction.


Assuntos
Proteína ADAMTS13/química , Proteína ADAMTS13/metabolismo , Fator de von Willebrand/química , Fator de von Willebrand/metabolismo , Sítios de Ligação , Fenômenos Biomecânicos , Cátions , Células HEK293 , Humanos , Cinética , Ligação Proteica , Domínios Proteicos
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