Domain tethering impacts dimerization and DNA-mediated allostery in the human transcription factor FoxP1.

Transcription factors are multidomain proteins with specific DNA binding and regulatory domains. In the human FoxP subfamily (FoxP1, FoxP2, FoxP3, and FoxP4) of transcription factors, a 90 residue-long disordered region links a Leucine Zipper (ZIP)-known to form coiled-coil dimers-and a Forkhead (FKH) domain-known to form domain swapping dimers. We used replica exchange discrete molecular dynamics simulations, single-molecule fluorescence experiments, and other biophysical tools to understand how domain tethering in FoxP1 impacts dimerization at ZIP and FKH domains and how DNA binding allosterically regulates their dimerization. We found that domain tethering promotes FoxP1 dimerization but inhibits a FKH domain-swapped structure. Furthermore, our findings indicate that the linker mediates the mutual organization and dynamics of ZIP and FKH domains, forming closed and open states with and without interdomain contacts, thus highlighting the role of the linkers in multidomain proteins. Finally, we found that DNA allosterically promotes structural changes that decrease the dimerization propensity of FoxP1. We postulate that, upon DNA binding, the interdomain linker plays a crucial role in the gene regulatory function of FoxP1.

Native and modified starches from underutilized seeds: Characteristics, functional properties and potential applications.

Seeds represent a potential source of starch, containing at least 60-70% of total starch, however many of them are treated as waste and are usually discarded. The review aim was to analyze the characteristics, functional properties, and potential applications of native and modified starches from underutilized seeds such as Sorghum bicolor L. Moench (WSS), Chenopodium quinoa, Wild. (QSS), Mangifera indica L. (MSS), Persea americana Mill. (ASS), Pouteria campechiana (Kunth) Baehni (PCSS), and Brosimum alicastrum Sw. (RSS). A systematic review of scientific literature was carried out from 2014 to date. Starch from seeds had yields above 30%. ASS had the higher amylose content and ASS and RSS showed the highest values in water absorption capacity and swelling power, contrary to MSS and PCSS while higher thermal resistance, paste stability, and a lower tendency to retrograde were observed in MSS and RSS. Functional properties such as water solubility, swelling power, thermal stability, low retrogradation tendency, and emulsion stability were increased in RSS, WSS, QSS, and MSS with chemical modifications (Oxidation, Oxidation-Crosslinking, OSA, DDSA, and NSA) and physical methods (HMT and dry-heat). Digestibility in vitro showed that WSS and QSS presented high SDS fraction, while ASS, MSS, PCSS, and HMT-QSS presented the highest RS content. Native or modified underutilized seed starches represent an alternative and sustainable source of non-conventional starch with potential applications in the food industry and for the development of healthy foods or for special nutritional requirements.

Starch Structure Influences Its Digestibility: A Review.

Twenty-five years ago, it was found that a significant fraction of the starch present in foods is not digested in the small intestine and continues to the large intestine, where it is fermented by the microbiota; this fraction was named resistant starch (RS). It was also reported that there is a fraction of starch that is slowly digested, sustaining a release of glucose in the small intestine. Later, health benefits were found to be associated with the consumption of this fraction, called slowly digestible starch (SDS). The authors declare both fractions to be "nutraceutical starch." An overview of the structure of both fractions (RS and SDS), as well as their nutraceutical characteristics, is presented with the objective of suggesting methods and processes that will increase both fractions in starchy foods and prevent diseases that are associated with the consumption of glycemic carbohydrates.

A distinct 5' flanking var gene region regulates Plasmodium falciparum variant erythrocyte surface antigen expression in placental malaria.

The Plasmodium falciparum multigene var family codes for approximately 50 variant adhesive proteins expressed in a mutually exclusive manner at the surface of infected red blood cells (iRBCs). Switching expression of var genes can lead to fundamental changes in the adhesive and antigenic properties of iRBCs. For example, a specific phenotypic switch in adhesion from CD36 to chondroitin sulphate A (CSA) is associated with malaria pathogenesis in pregnant women. The factors and DNA elements that control the expression of a particular member of the var gene family during gestational malaria remains enigmatic. Here, we report that the subtelomeric FCR3 varCSA is expressed under the control of a unique DNA element of 1.8 kb, whereas the other members of the var multigene family are flanked by common regulatory elements. The 5' varCSA-type element is conserved as a single copy in laboratory strains and clinical isolates from Brazil and West Africa and contains two distinct repetitive elements of 150 bp and 60 bp respectively. The 5' varCSA-type sequence tags a var gene in the 3D7 genome that is homologous to the FCR3 varCSA gene. A recombinant DBL gamma domain of this var gene showed specific binding to CSA. This subtelomeric varCSA gene is transcribed in the opposite sense when compared with the usual orientation of telomere-adjacent var genes. This unique arrangement might explain why the varCSA gene is relatively conserved in genetically distinct parasites despite being located in a highly recombinogenic chromosome compartment. The 5' untranslated region (UTR) of the varCSA-type sequence is also transcribed in placental isolates that bind to CSA, illustrating an important role for the unique 5' varCSA-type sequence in the regulation of var genes involved in malaria pathogenesis in pregnant women. However, this promoter is not always found to be transcribing var genes selected for expression of products that bind to CSA in vitro. Our work identifies a sequence tag for the identification of varCSA genes in placental isolates for the first time.