RESUMO
OBJECTIVE: To analyze postoperative complications of totally implantable central venous port system (TIPCVP) deployment and develop methods of their prevention. MATERIAL AND METHODS: The study involved 43 patients who underwent TIPCVP implantation through right-sided jugular access and 3 patients with migration of the catheter transferred to the Domodedovo Central City Hospital. RESULTS: There were four perioperative and one early postoperative complication. None of the complications was the reason for removal of TIPCVP. Pinch-off syndrome occurred in two patients who were operated in other hospitals and a catheter was inserted through the right subclavian vein. CONCLUSION: Injury of the carotid artery and pneumothorax can be avoided by ultrasound navigation during internal jugular vein puncture. Catheterization of the internal jugular vein is useful to avoid pinch-off syndrome. Migration of the catheter is successfully cured by endovascular methods.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Pneumotórax/prevenção & controle , Cateterismo Venoso Central/métodos , Cateteres de Demora/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Remoção de Dispositivo , Migração de Corpo Estranho/etiologia , Migração de Corpo Estranho/terapia , Humanos , Veias Jugulares/diagnóstico por imagem , Veias Jugulares/lesões , Pneumotórax/etiologia , Veia Subclávia/diagnóstico por imagem , Ultrassonografia de IntervençãoRESUMO
It is presented the detailed description with illustrations of 3 surgical accesses which are used by authors to dissect retroperitoneal organs and anatomic structures in victims with closed trauma and abdominal injury. We reported clinical observations of successful use of developed accesses.
Assuntos
Traumatismos Abdominais/cirurgia , Laparotomia/métodos , Traumatismo Múltiplo , Espaço Retroperitoneal/cirurgia , Ferimentos não Penetrantes/cirurgia , Adulto , Feminino , Humanos , MasculinoAssuntos
Traumatismos Abdominais , Rim/lesões , Ferimentos não Penetrantes , Traumatismos Abdominais/diagnóstico , Traumatismos Abdominais/etiologia , Traumatismos Abdominais/fisiopatologia , Traumatismos Abdominais/terapia , Gerenciamento Clínico , Humanos , Rim/diagnóstico por imagem , RadiografiaAssuntos
Traumatismos Abdominais/complicações , Erros de Diagnóstico/prevenção & controle , Laparotomia/métodos , Pâncreas , Pancreatectomia , Ferimentos não Penetrantes/complicações , Colangiopancreatografia por Ressonância Magnética/métodos , Tratamento Conservador , Diagnóstico Precoce , Humanos , Tomografia Computadorizada Multidetectores/métodos , Pâncreas/diagnóstico por imagem , Pâncreas/lesões , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Seleção de PacientesRESUMO
A recent crystal structure of the N15 alpha/beta-T cell receptor (TCR) in complex with an Fab derived from the H57 Cbeta-specific monoclonal antibody (mAb) shows the mAb fragment interacting with the elongated FG loop of the Cbeta domain. This loop creates one side wall of a cavity within the TCR Ti-alpha/beta constant region module (CalphaCbeta) while the CD and EF loops of the Calpha domain form another wall. The cavity size is sufficient to accommodate a single nonglycosylated Ig domain such as the CD3epsilon ectodomain. By using specific mAbs to mouse TCR-beta (H57) and CD3epsilon (2C11) subunits, we herein provide evidence that only one of the two CD3epsilon chains within the TCR complex is located in close proximity to the TCR Cbeta FG loop, in support of the above notion. Moreover, analysis of T cells isolated from transgenic mice expressing both human and mouse CD3epsilon genes shows that the heterologous human CD3epsilon component can replace the mouse CD3epsilon at this site. The location of one CD3epsilon subunit within the rigid constant domain module has implications for the mechanism of signal transduction throughout T cell development.
Assuntos
Complexo CD3/química , Receptores de Antígenos de Linfócitos T/química , Animais , Anticorpos Monoclonais/química , Sítios de Ligação/imunologia , Citometria de Fluxo , Humanos , Camundongos , Camundongos Transgênicos , Modelos Moleculares , Transdução de Sinais/imunologia , Baço/imunologia , Linfócitos T/fisiologiaAssuntos
Traumatismos Abdominais , Hepatectomia/métodos , Laparotomia/métodos , Fígado/lesões , Ferimentos não Penetrantes , Traumatismos Abdominais/diagnóstico , Traumatismos Abdominais/epidemiologia , Traumatismos Abdominais/cirurgia , Saúde Global , Humanos , Incidência , Índices de Gravidade do Trauma , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/epidemiologia , Ferimentos não Penetrantes/cirurgiaRESUMO
The adhesion domain of human CD2 bears a single N-linked carbohydrate. The solution structure of a fragment of CD2 containing the covalently bound high-mannose N-glycan [-(N-acetylglucosamine)2-(mannose)5-8] was solved by nuclear magnetic resonance. The stem and two of three branches of the carbohydrate structure are well defined and the mobility of proximal glycan residues is restricted. Mutagenesis of all residues in the vicinity of the glycan suggests that the glycan is not a component of the CD2-CD58 interface; rather, the carbohydrate stabilizes the protein fold by counterbalancing an unfavorable clustering of five positive charges centered about lysine-61 of CD2.
Assuntos
Antígenos CD2/química , Oligossacarídeos/química , Conformação Proteica , Acetilglucosamina/química , Sequência de Aminoácidos , Animais , Antígenos CD/metabolismo , Sítios de Ligação , Antígenos CD2/metabolismo , Antígenos CD58 , Células CHO , Configuração de Carboidratos , Sequência de Carboidratos , Adesão Celular , Cricetinae , Glicosilação , Humanos , Espectroscopia de Ressonância Magnética , Glicoproteínas de Membrana/metabolismo , Dados de Sequência Molecular , Mutagênese Sítio-DirigidaRESUMO
The crystal structure of a complex involving the D10 T cell receptor (TCR), 16-residue foreign peptide antigen, and the I-Ak self major histocompatibility complex (MHC) class II molecule is reported at 3.2 angstrom resolution. The D10 TCR is oriented in an orthogonal mode relative to its peptide-MHC (pMHC) ligand, necessitated by the amino-terminal extension of peptide residues projecting from the MHC class II antigen-binding groove as part of a mini beta sheet. Consequently, the disposition of D10 complementarity-determining region loops is altered relative to that of most pMHCI-specific TCRs; the latter TCRs assume a diagonal orientation, although with substantial variability. Peptide recognition, which involves P-1 to P8 residues, is dominated by the Valpha domain, which also binds to the class II MHC beta1 helix. That docking is limited to one segment of MHC-bound peptide offers an explanation for epitope recognition and altered peptide ligand effects, suggests a structural basis for alloreactivity, and illustrates how bacterial superantigens can span the TCR-pMHCII surface.
Assuntos
Antígenos/química , Antígenos de Histocompatibilidade Classe II/química , Receptores de Antígenos de Linfócitos T alfa-beta/química , Animais , Antígenos/imunologia , Antígenos/metabolismo , Sítios de Ligação , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Conalbumina/química , Conalbumina/imunologia , Cristalização , Cristalografia por Raios X , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Ligação de Hidrogênio , Ligantes , Camundongos , Camundongos Endogâmicos AKR , Modelos Moleculares , Oligopeptídeos/química , Oligopeptídeos/imunologia , Oligopeptídeos/metabolismo , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Superantígenos/imunologia , Superantígenos/metabolismo , Timo/citologia , Timo/imunologiaRESUMO
Whether T-cell receptors (TCRs) recognize antigenic peptides bound to major histocompatability complex (MHC) molecules through common or distinct docking modes is currently uncertain. We report the crystal structure of a complex between the murine N15 TCR [1-4] and its peptide-MHC ligand, an octapeptide fragment representing amino acids 52-59 of the vesicular stomatitis virus nuclear capsid protein (VSV8) bound to the murine H-2Kb class I MHC molecule. Comparison of the structure of the N15 TCR-VSV8-H-2Kb complex with the murine 2C TCR-dEV8-H-2Kb [5] and the human A6 TCR-Tax-HLA-A2 [6] complexes revealed a common docking mode, regardless of TCR specificity or species origin, in which the TCR variable Valpha domain overlies the MHC alpha2 helix and the Vbeta domain overlies the MHC alpha1 helix. As a consequence, the complementary determining regions CDR1 and CDR3 of the TCR Valpha and Vbeta domains make the major contacts with the peptide, while the CDR2 loops interact primarily with the MHC. Nonetheless, in terms of the details of the relative orientation and disposition of binding, there is substantial variation in TCR parameters, which we term twist, tilt and shift, and which define the variation of the V module of the TCR relative to the MHC antigen-binding groove.
Assuntos
Antígenos de Histocompatibilidade/química , Peptídeos/química , Receptores de Antígenos de Linfócitos T alfa-beta/química , Animais , Sítios de Ligação , Capsídeo/química , Capsídeo/metabolismo , Cristalografia por Raios X , Produtos do Gene tax/química , Produtos do Gene tax/metabolismo , Antígenos H-2/química , Antígenos H-2/metabolismo , Antígeno HLA-A2/química , Antígeno HLA-A2/metabolismo , Antígenos de Histocompatibilidade/metabolismo , Humanos , Técnicas In Vitro , Substâncias Macromoleculares , Camundongos , Modelos Moleculares , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Peptídeos/metabolismo , Conformação Proteica , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Vírus da Estomatite Vesicular Indiana/química , Vírus da Estomatite Vesicular Indiana/metabolismoRESUMO
CD2 mediates interaction between T cells and their cognate partners through its CD58-binding membrane-distal adhesion domain (D1) facilitating T cell receptor (TCR) triggering. A neoepitope defined by anti-CD2R monoclonal antibodies (mAbs) has suggested structural alteration within the CD2 ectodomain during T cell activation. Here, we map CD2R to the flexible CD2 linker region between D1 and the membrane-proximal extracellular domain (D2) and show that exposure of this conformational site is independent of temperature and metabolic energy. Co-ligation of CD2 and CD58 molecules on opposing cells within a conjugate pair induces CD2R and redistributes CD2 to the region of cell-cell contact. These CD2R+ molecules, in contrast to the CD2R-molecules, are tightly clustered on the T cell surface. Hence, a ligand-mediated increase in the D1-D2 interdomain angle apparently exposes CD2R, facilitates packing of CD2 molecules in a clustered array and is linked to CD2-mediated adhesion and activation events. Conformational alteration of this type may be generally important in ordered lattice formation involving surface receptors.
Assuntos
Antígenos CD2/metabolismo , Mapeamento de Epitopos , Receptores Imunológicos/metabolismo , Antígenos CD2/imunologia , Adesão Celular , Linhagem Celular , Humanos , Ligantes , Mutação , Conformação Proteica , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Linfócitos T/imunologiaRESUMO
The molecular interactions between the CD8 co-receptor dependent N15 and N26 T cell receptors (TCRs) and their common ligand, the vesicular stomatitis virus octapeptide (VSV8) bound to H-2Kb, were studied to define the docking orientation(s) of MHC class I restricted TCRs during immune recognition. Guided by the molecular surfaces of the crystallographically defined peptide/MHC and modeled TCRs, a series of mutations in exposed residues likely contacting the TCR ligand were analyzed for their ability to alter peptide-triggered IL-2 production in T cell transfectants. Critical residues which diminished antigen recognition by 1000 to 10,000-fold in molar terms were identified in both N15 Valpha (alphaE94A or alphaE94R, Y98A and K99) and Vbeta (betaR96A, betaW97A and betaD99A) CDR3 loops. Mutational analysis indicated that the Rp1 residue of VSV8 is critical for antigen recognition of N15 TCR, but R62 of H-2Kb is less critical. More importantly, the alphaE94R mutant could be fully complemented by a reciprocal charge reversal at Kb R62 (R62E). This result suggests a direct interaction between N15 TCR Valpha E94R and Kb R62E residues. As Rp1 of VSV8 is adjacent to R62 in the VSV8/Kb complex and essential for T cell activation, this orientation implies that the N15 Valpha CDR3 loop interacts with the N-terminal residues of VSV8 with the Valpha domain docking to the Kb alpha2 helix while the N15 Vbeta CDR3 loop interacts with the more C-terminal peptide residues and the Vbeta domain overlies the Kb alpha1 helix. An equivalent orientation is suggested for N26, a second VSV8/Kb specific TCR. Given that genetic analysis of two different class II MHC-restricted TCRs and two crystallographic studies of class I restricted TCRs offers a similar overall orientation of V domains relative to alpha-helices, these data raise the possibility of a common docking mode between TCRs and their ligands regardless of MHC restriction.
Assuntos
Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Conformação Proteica , Receptores de Antígenos de Linfócitos T alfa-beta/química , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Células Apresentadoras de Antígenos/imunologia , Sítios de Ligação , Linfócitos T CD8-Positivos/imunologia , Clonagem Molecular , Cristalografia por Raios X , Humanos , Interleucina-2/biossíntese , Linfoma de Células B , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação Puntual , Reação em Cadeia da Polimerase , Estrutura Secundária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transfecção , Células Tumorais CultivadasRESUMO
Recent mutations of the 5-hydroxytryptamine (5-HT)1B and 5-HT1D receptor subtypes suggest that a threonine in the seventh transmembrane helix may be responsible for the selectivity of these receptors. A molecular dynamics simulation of a three-dimensional model of the 5-HT1D receptor interacting with a selective agonist, sumatriptan, shows that, although Thr342 in helix 7 does not have a direct interaction with sumatriptan, it contributes to the selectivity of this receptor through an indirect mechanism. The hydrogen bond between O gamma-H of Thr342 and the backbone C = O of Phe338 stabilizes a bent conformation of the helix that is formed due to the interaction between sumatriptan and Asp339 at one end and Tyr346 at the other end. The indirect mechanism may explain the small change in the affinity for the selective agonist sumatriptan of the receptor in which Thr342 was mutated to asparagine.
Assuntos
Estrutura Secundária de Proteína , Receptores de Serotonina/química , Receptores de Serotonina/metabolismo , Treonina/química , Treonina/metabolismo , Sítios de Ligação , Humanos , Ligação de Hidrogênio , Ligantes , Substâncias Macromoleculares , Modelos Químicos , Mutação/fisiologia , Receptores de Serotonina/genética , TermodinâmicaRESUMO
Recent evidence indicates that CD4 stably binds to major histocompatibility complex (MHC) class II only after assuming an oligomeric state: the membrane-distal CD4 D1-D2 module interacts directly with MHC class II, whereas the membrane-proximal CD4 D3-D4 module mediates oligomerization. This results in the formation of aggregates critical for T-cell activation. The T-cell receptor (TCR) regulates specific crosslinking and is itself dependent on lattice formation to trigger physiological T-cell responses. Here, Toshiko Sakihama, Alex Smolyar and Ellis Reinherz discuss the molecular nature of CD4-MHC class II clustering and how, despite each of the component interactions being of low affinity, the molecular matrix renders T-cell recognition extremely specific and sensitive.
Assuntos
Apresentação de Antígeno , Antígenos CD4 , Antígenos de Histocompatibilidade Classe II , Receptores de Antígenos de Linfócitos T , Animais , Antígenos CD4/química , Antígenos CD4/metabolismo , Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/metabolismoRESUMO
Previous studies have failed to detect an interaction between monomeric soluble CD4 (sCD4) and class II major histocompatibility complex (MHC) proteins, suggesting that oligomerization of CD4 on the cell surface may be required to form a stable class II MHC binding site. To test this possibility, we transfected the F43I CD4 mutant, which is incapable of binding to class II MHC or human immunodeficiency virus (HIV) gp120, into COS-7 cells together with wild-type CD4 (wtCD4). Expression of F43I results in a dominant negative effect: no class II MHC binding is observed even though wtCD4 expression is preserved. Apparently, F43I associates with wtCD4 oligomers and interferes with the formation of functional class II MHC binding structures. In contrast, F43I does not affect the binding of gp120 to wtCD4, implying that gp120 binds to a CD4 monomer. By production and characterization of chimeric CD4 molecules, we show that domains 3 and/or 4 appear to be involved in oligomerization. Several models of the CD4-class II MHC interaction are offered, including the possibility that one or two CD4 molecules initially interact with class II MHC dimers and further associate to create larger complexes important for facilitating T-cell receptor crosslinking.
Assuntos
Antígenos CD4/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , Antígenos HLA-D/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Linfócitos T/imunologia , Animais , Antígenos CD4/biossíntese , Antígenos CD4/química , Linhagem Celular , Chlorocebus aethiops , Citometria de Fluxo , Proteína gp120 do Envelope de HIV/imunologia , Antígenos HLA-D/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Ativação Linfocitária , Substâncias Macromoleculares , Modelos Imunológicos , Ligação Proteica , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Transfecção , Células Tumorais CultivadasRESUMO
We have characterized a novel cDNA whose steady state mRNA levels rise in the thymus 2 to 6 h following the induction of CD4+CD8+ thymocyte apoptosis by in vivo cross-linking of CD3 epsilon. This cDNA, AND-34-1, contains an open reading frame (ORF) encoding a protein with an amino-terminal Src homology 2 (SH2) domain and a carboxyl-terminal domain homologous to GDP-exchange factors (GEFs). Northern analysis demonstrates widespread expression of the AND-34 gene. Anti-CD3 epsilon treatment induces up-regulation of the AND-34 mRNA levels in total thymic RNA but not in RNA from purified thymocytes, suggesting that this transcript is derived from a thymic stromal cell population. IL-1 and TNF increase AND-34 transcript levels in thymic cortical reticular, thymic nurse, and fibroblast cell lines. In the thymic cortical reticular cell line, IL-1 and TNF induce a protein of the predicted 93-kDa size reactive with anti-AND-34 peptide antisera. Fifteen minutes of serum stimulation of vanadate-pretreated AND-34-1-transfected NIH3T3 fibroblasts induces tyrosine phosphorylation of AND-34 as well as coprecipitating 95-, 125-, and 130-kDa proteins. One of these tyrosine phosphorylated proteins is identified as p130Cas (Crk-associated substrate), a signaling molecule previously known to bind to a GDP-exchange factor (C3G) and inducibly associate with the focal adhesion complex. Consistent with such an association, AND-34 tyrosine phosphorylation is induced following adherence of trypsinized fibroblasts to fibronectin or poly-L -lysine-coated surfaces.
Assuntos
Citocinas/fisiologia , Fatores de Troca do Nucleotídeo Guanina , Fosfoproteínas/metabolismo , Proteínas/metabolismo , Timo/metabolismo , Células 3T3 , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Aminoácidos , Animais , Sequência de Bases , Adesão Celular/imunologia , Proteínas de Ciclo Celular/química , Proteína Substrato Associada a Crk , Interleucina-1/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fosforilação , Reação em Cadeia da Polimerase , Testes de Precipitina , Ligação Proteica/imunologia , Proteínas/química , Proteínas/genética , Proteínas/isolamento & purificação , Proteína p130 Retinoblastoma-Like , Homologia de Sequência de Aminoácidos , Células Estromais/imunologia , Células Estromais/metabolismo , Timo/citologia , Timo/imunologia , Fator de Necrose Tumoral alfa/fisiologia , Tirosina/metabolismo , ras-GRF1RESUMO
Small ligands generally bind within the seven transmembrane-spanning helices of G-protein-coupled receptors, but their access to the binding pocket through the closely packed loops has not been elucidated. In this work, a model of the extracellular loops of the thyrotropin-releasing hormone (TRH) receptor (TRHR) was constructed, and molecular dynamics simulations and quasi-harmonic analysis have been performed to study the static and dynamic roles of the extracellular domain. The static analysis based on curvature and electrostatic potential on the surface of TRHR suggests the formation of an initial recognition site between TRH and the surface of its receptor. These results are supported by experimental evidence. A quasi-harmonic analysis of the vibrations of the extracellular loops suggest that the low-frequency motions of the loops will aid the ligand to access its transmembrane binding pocket. We suggest that all small ligands may bind sequentially to the transmembrane pocket by first interacting with the surface binding site and then may be guided into the transmembrane binding pocket by fluctuations in the extracellular loops.
Assuntos
Estrutura Secundária de Proteína , Receptores do Hormônio Liberador da Tireotropina/química , Receptores do Hormônio Liberador da Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação , Células COS , Clonagem Molecular , Simulação por Computador , Sequência Conservada , Proteínas de Ligação ao GTP/metabolismo , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Software , Hormônio Liberador de Tireotropina/química , TransfecçãoRESUMO
The surface residues of the VSV8/Kb complex important for recognition by N15 and N26 alphabeta T cell receptors (TCR) were mapped by mutational analysis and compared to each other and with epitopes of well-characterized Kb specific monoclonal antibodies (mAb). Three features of immune receptor recognition emerge. First, the footprints of the two TCR on VSV8/Kb are similar with more than 80 % overlap between sites. Given that only 8 of 14 surface exposed VSV8/Kb residues identified as critical for TCR interaction are in common, the chemical basis of the N15 and N26 interactions is nevertheless distinct. Second, the cognate peptide is a major focus of TCR recognition: mutation at any of the three exposed side chains (at p1, p4 or p6) abrogates interaction of both TCR as measured by functional T cell activation. Third, in contrast to TCR, mAb bind to discrete segments on the periphery of the alpha1 and/or alpha2 helices without orientational restriction. These findings suggest that unlike soluble antibodies, surface membrane receptor-ligand interactions on opposing cells (i.e. TCR-peptide/ MHC, CD8-MHC) limit the orientational freedom of the TCR in the immune recognition process.
Assuntos
Antígenos Virais/imunologia , Antígenos H-2/fisiologia , Receptores de Antígenos de Linfócitos T/química , Vírus da Estomatite Vesicular Indiana/imunologia , Animais , Anticorpos Monoclonais/imunologia , Mapeamento de Epitopos , Camundongos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Peptídeos/imunologia , Conformação Proteica , Transdução de Sinais , Relação Estrutura-AtividadeRESUMO
Interaction between CD2 and its counterreceptor, CD58 (LFA-3), on opposing cells optimizes immune recognition, facilitating contacts between helper T lymphocytes and antigen-presenting cells as well as between cytolytic effectors and target cells. Here, we report the crystal structure of the heterophilic adhesion complex between the amino-terminal domains of human CD2 and CD58. A strikingly asymmetric, orthogonal, face-to-face interaction involving the major beta sheets of the respective immunoglobulin-like domains with poor shape complementarity is revealed. In the virtual absence of hydrophobic forces, interdigitating charged amino acid side chains form hydrogen bonds and salt links at the interface (approximately 1200 A2), imparting a high degree of specificity albeit with low affinity (K(D) of approximately microM). These features explain CD2-CD58 dynamic binding, offering insights into interactions of related immunoglobulin superfamily receptors.
Assuntos
Antígenos CD2/química , Antígenos CD58/química , Sequência de Aminoácidos , Animais , Antígenos CD2/metabolismo , Antígenos CD58/metabolismo , Moléculas de Adesão Celular/química , Cristalografia por Raios X , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Ratos , Homologia de Sequência de AminoácidosRESUMO
The crystal structure of the two immunoglobulin variable-like domains of the murine CD8alphaalpha homodimer complexed to the class I MHC H-2Kb molecule at 2.8 A resolution shows that CD8alphaalpha binds to the protruding MHC alpha3 domain loop in an antibody-like manner. Comparison of mouse CD8alphaalpha/H-2Kb and human CD8alphaalpha/HLA-A2 complexes reveals shared as well as species-specific recognition features. In both species, coreceptor function apparently involves the participation of CD8 dimer in a bidentate attachment to an MHC class I molecule in conjunction with a T cell receptor without discernable conformational alteration of the peptide or MHC antigen-presenting platform.