Amino acid repeat signatures underlying human-pathogen interactions
Description
Emerging evidence suggests that amino acid homorepeats (HRs) in proteins (HRPs) contribute to protein interactability. What is the role of HRs in human-pathogen protein interactions? We find that pathogens engage physiologically important human HRPs, thereby affecting diverse host physiological processes. From the pathogen standpoint, (i) eukaryotic pathogens engage more HRPs but with host-sparse HRs, leading to disparate and discriminate interactions, (ii) prokaryotic pathogens engage less HRPs but with host-abundant non-polar HRs via host protein proxies bringing about discriminate or promiscuous interactions and (iii) viral pathogens engage more HRPs with host-abundant polar uncharged HRs affecting promiscuous interactions using host-partner HR tract mimicry. To propel further research, we introduce a resource Hi-PHI (http://hiphi.iisertirupati.ac.in/) cataloging critical information about human and pathogen HRPs and HRs. We propose mechanisms to (i) repurpose drugs targeting human HRPs engaged by pathogens for treating different infections and (ii) exploit HRs and their flanks as targets for pathogen-targeted anti-infectives. Here, we have uploaded the assembled and curated human-pathogen protein interactome (HPI), which has 19,535 interactions between human and pathogen proteins. We have also provided the source code to facilitate repetition of this work and address other fundamental systems- and molecular-level questions. The instructions regarding usage of the codes are provided in individual scripts. All the datasets assembled, curated, generated and used in this study is available as a resource, Hi-PHI database (http://hiphi.iisertirupati.ac.in/).