Atomic Structure of the Leishmania spp Hsp100 N-domain

Authors

Jonathan M Mercado
Sukyeong Lee
Changsoo Chang
Nuri Sung
Lynn Soong
Andre Catic
Francis T F Tsai

Publication Date

6-1-2022

Journal

Proteins

DOI

10.1002/prot.26310

PMID

35122310

PMCID

PMC9018533

PubMedCentral® Posted Date

12-1-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Binding Sites, Heat-Shock Proteins, Humans, Peptides, Leishmania, Molecular chaperone, Protein unfoldase, Hsp100

Abstract

Hsp100 is an ATP-dependent unfoldase that promotes protein disaggregation or facilitates the unfolding of aggregation-prone polypeptides marked for degradation. Recently, new Hsp100 functions are emerging. In Plasmodium, an Hsp100 drives malaria protein export, presenting a novel drug target. Whether Hsp100 has a similar function in other protists is unknown. We present the 1.06 Å resolution crystal structure of the Hsp100 N-domain from Leishmania spp., the causative agent of leishmaniasis in humans. Our structure reveals a network of methionines and aromatic amino acids that define the putative substrate-binding site and likely evolved to protect Hsp100 from oxidative damage in host immune cells.

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