Reassessing the exon-foldon correspondence using frustration analysis

• 成果类型: Article
• 署名作者: Galpern, Ezequiel A.; Jaafari, Nana; Bueno, Carlos; Wolynes, Peter G.; Ferreiro, Diego U.
• 署名单位: University of Buenos Aires; University of Buenos Aires; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Rice University; Rice University; Rice University; Rice University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15149
• DOI: 10.1073/pnas.2400151121
• 发表日期: 2024-07-09
• 关键词: secondary structure; protein; genes; units; RECOGNITION; database

摘要

Protein folding and evolution are intimately linked phenomena. Here, we revisit the concept of exons as potential protein folding modules across a set of 38 abundant and conserved protein families. Taking advantage of genomic exon-intron organization and extensive protein sequence data, we explore exon boundary conservation and assess the foldon-like behavior of exons using energy landscape theoretic measurements. We found deviations in the exon size distribution from exponential decay indicating selection in evolution. We show that when taken together there is a pronounced tendency to independent foldability for segments corresponding to the more conserved exons, supporting the idea of exon-foldon correspondence. While 45% of the families follow this general trend when analyzed individually, there are some families for which other stronger functional determinants, such as preserving frustrated active sites, may be acting. We further develop a systematic partitioning of protein domains using exon boundary hotspots, showing that minimal common exons correspond with uninterrupted alpha and/or beta elements for the majority of the families but not for all of them.