Bacteria use structural imperfect mimicry to hijack the host interactome
Sánchez de Groot, Natalia (Centre de Regulació Genòmica)
Torrent Burgas, Marc (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2020
Abstract:	Bacteria use protein-protein interactions to infect their hosts and hijack fundamental pathways, which ensures their survival and proliferation. Hence, the infectious capacity of the pathogen is closely related to its ability to interact with host proteins. Here, we show that hubs in the host-pathogen interactome are isolated in the pathogen network by adapting the geometry of the interacting interfaces. An imperfect mimicry of the eukaryotic interfaces allows pathogen proteins to actively bind to the host's target while preventing deleterious effects on the pathogen interactome. Understanding how bacteria recognize eukaryotic proteins may pave the way for the rational design of new antibiotic molecules. To fulfil their function, proteins need to interact with each other forming complexes. Understanding how pathogen proteins bind their host counterparts is important to explain how bacteria can infect, survive and proliferate inside cells. To achieve that, pathogen proteins mimic eukaryote interfaces to interact with the host. However, we discovered that such mimicry is imperfect, and pathogen proteins display particular features that are not found in eukaryotic complexes. This imperfect mimicry would allow pathogen proteins to actively bind to the host targets while preventing deleterious effects on the pathogen network. Indeed, we show that highly connected proteins (hubs) in the host-pathogen networks are mostly isolated in the pathogen network. The existence of imperfect mimicry opens the door to the design of new molecules aimed to target host-pathogen complexes with reduced side effects. Hence, in the long term, our results may lay the foundation of a new class of antimicrobials.
Grants:	Ministerio de Economía y Competitividad RYC-2012-09999 Ministerio de Economía y Competitividad SAF2015-72518-EXP Agencia Estatal de Investigación SAF2017-82158-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PLoS computational biology, Vol. 16 (December 2020) , art. e1008395, ISSN 1553-7358

DOI: 10.1371/journal.pcbi.1008395
PMID: 33275611

17 p, 2.3 MB

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