Toggle Main Menu Toggle Search

Open Access padlockePrints

Structural comparison strengthens the higher-order classification of proteases related to chymotrypsin

Lookup NU author(s): Heli Monttinen

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2019 Mönttinen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Specific cleavage of proteins by proteases is essential for several cellular, physiological, and viral processes. Chymotrypsin-related proteases that form the PA clan in the MEROPS classification of proteases is one of the largest and most diverse group of proteases. The PA clan comprises serine proteases from bacteria, eukaryotes, archaea, and viruses and chymotrypsin-related cysteine proteases from positive-strand RNA viruses. Despite low amino acid sequence identity, all PA clan proteases share a conserved double β-barrel structure. Using an automated structure-based hierarchical clustering method, we identified a common structural core of 72 amino acid residues for 143 PA clan proteases that represent 12 protein families and 11 subfamilies. The identified core is located around the catalytic site between the two β-barrels and resembles the structures of the smallest PA clan proteases. We constructed a structure-based distance tree derived from the properties of the identified common core. Our structure-based analyses support the current classification of these proteases at the subfamily level and largely at the family level. Structural alignment and structure-based distance trees could thus be used for directing objective classification of PA clan proteases and to strengthen their higher order classification. Our results also indicate that the PA clan proteases of positive-strand RNA viruses are related to cellular heatshock proteases, which suggests that the exchange of protease genes between viruses and cells might have occurred more than once.


Publication metadata

Author(s): Monttinen HAM, Ravantti JJ, Poranen MM

Publication type: Article

Publication status: Published

Journal: PLoS ONE

Year: 2019

Volume: 14

Issue: 5

Online publication date: 17/05/2019

Acceptance date: 25/04/2019

Date deposited: 13/06/2019

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pone.0216659

DOI: 10.1371/journal.pone.0216659

PubMed id: 31100077


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
170046
250113
272507
Jenny and Antti Wihuri Foundation
Oskari Huttunen foundation
Sigrid Juselius Foundation

Share