title: What can we learn from highly connected beta-rich structures for structural interface design?
abstract: Most hubs' binding sites are able to transiently interact with numerous proteins. We focus on beta-rich hubs with the goal of inferring features toward design. Since they are able to interact with many partners and association of beta-conformations may lead to amyloid fibrils, we ask whether there is some property that distinguishes them from low-connectivity beta-rich proteins, which may be more interaction specific. Identification of such features should be useful as they can be incorporated in interface design while avoiding polymerization into fibrils. We classify the proteins in the yeast interaction map according to the types of their secondary structures. The small number of the obtained beta-rich protein structures in the Protein Data Bank likely reflects their low occurrence in the proteome. Analysis of the obtained structures indicates that highly connected beta-rich proteins tend to have clusters of conserved residues in their cores, unlike beta-rich structures with low connectivity, suggesting that the highly packed conserved cores are important to the stability of proteins, which have residue composition and sequence prone to beta-structure and amyloid formation. The enhanced stability may hinder partial unfolding, which, depending on the conditions, is more likely to lead to polymerization of these sequences.
authors.affiliation: Polymer Research Center and Chemical Engineering Department, Bogaziçi University, Istanbul, Turkey.
authors.forename: Ugur
authors.initials: U
authors.lastname: Emekli
authors.forename: K
authors.initials: K
authors.lastname: Gunasekaran
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Turkan
authors.initials: T
authors.lastname: Haliloglu
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D020543:Proteome / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*
chemical_list: D000682:Amyloid; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins