Domain swapping in proteins is an important mechanism of functional and structural innovation. However, despite its ubiquity and importance, the physical mechanisms that lead to domain swapping are poorly understood. Here, we present a simple two-dimensional coarse-grained model of protein domain swapping in the cytoplasm. In our model, two-domain proteins partially unfold and diffuse in continuous space. Monte Carlo multiprotein simulations of the model reveal that domain swapping occurs at intermediate temperatures, whereas folded dimers and folded monomers prevail at low temperatures, and partially unfolded monomers predominate at high temperatures. We use a simplified amino acid alphabet consisting of four residue types, and find that the oligomeric state at a given temperature depends on the sequence of the protein. We also show that hinge strain between domains can promote domain swapping, consistent with experimental observations for real proteins. Domain swapping depends nonmonotonically on the protein concentration, with domain-swapped dimers occurring at intermediate concentrations and nonspecific interactions between partially unfolded proteins occurring at high concentrations. For folded proteins, we recover the result obtained in three-dimensional lattice simulations, i.e., that functional dimerization is most prevalent at intermediate temperatures and nonspecific interactions increase at low temperatures.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906159 | PMC |
http://dx.doi.org/10.1016/j.bpj.2016.04.033 | DOI Listing |
ACS Cent Sci
January 2025
Institute of Organic Chemistry, Heidelberg University, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
The design of metalloproteins allows us to better understand metal complexation in proteins and the resulting function. In this study, we incorporated a Cu-binding site into a natural protein domain, the 58 amino acid c-Crk-SH3, to create a miniaturized superoxide dismutase model, termed SO1. The resulting low complexity metalloprotein was characterized for structure and function by circular dichroism and UV spectroscopy as well as EPR spectroscopy and X-ray crystallography.
View Article and Find Full Text PDFNat Plants
January 2025
National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.
Arabidopsis PHOSPHATE 1 (AtPHO1) and its closest homologue AtPHO1;H1 are phosphate transporters that load phosphate into the xylem vessel for root-to-shoot translocation. AtPHO1 and AtPHO1;H1 are prototypical members of the unique SPX-EXS family, whose structural and molecular mechanisms remain elusive. In this study, we determined the cryogenic electron microscopy structure of AtPHO1;H1 binding with inorganic phosphate (Pi) and inositol hexakisphosphate in a closed conformation.
View Article and Find Full Text PDFBiochem Biophys Res Commun
February 2025
San Francisco State University, Department of Chemistry and Biochemistry, San Francisco, CA, 94132, USA. Electronic address:
Enterococcus faecalis is a multi-drug-resistant human pathogen that is found in a variety of environments and is challenging to treat. Under stress conditions, some bacteria regulate intracellular polyamine concentrations via polyamine acetyltransferases to reduce their toxicity. The E.
View Article and Find Full Text PDFbioRxiv
January 2025
Ben-May Institute for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
Insulin degrading enzyme (IDE) is a dimeric 110 kDa M16A zinc metalloprotease that degrades amyloidogenic peptides diverse in shape and sequence, including insulin, amylin, and amyloid-β, to prevent toxic amyloid fibril formation. IDE has a hollow catalytic chamber formed by four homologous subdomains organized into two ~55 kDa N- and C- domains (IDE-N and IDE-C, respectively), in which peptides bind, unfold, and are repositioned for proteolysis. IDE is known to transition between a closed state, poised for catalysis, and an open state, able to release cleavage products and bind new substrate.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, D-66123 Saarbrücken, Germany; Deutsches Zentrum für Infektionsforschung (DZIF), Standort Hannover-Braunschweig; Department of Chemistry, PharmaScienceHub (PSH), Saarland University, D-66123 Saarbrücken, Germany.
Bacteria frequently employ carbohydrate-binding proteins, so-called lectins, to colonize and persist in a host. Thus, bacterial lectins are attractive targets for the development of new antiinfectives. To find new potential targets for antiinfectives against pathogenic bacteria, we searched for homologs of Pseudomonas aeruginosa lectins and identified homologs of LecA in Enterobacter species.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!