Conservation of structure and protein-protein interactions mediated by the secreted mycobacterial proteins EsxA, EsxB, and EspA

Callahan, Brian, Nguyen, Kiet, Collins, Alissa, Valdes, Kayla, Caplow, Michael, Crossman, David K, Steyn, Adrie J C, Eisele, Leslie and Derbyshire, Keith M (2010) Conservation of structure and protein-protein interactions mediated by the secreted mycobacterial proteins EsxA, EsxB, and EspA. Journal of Bacteriology, 192 (1). pp. 326-35. ISSN 0021-9193

Full text not available from this repository.

Abstract

Mycobacterium tuberculosis EsxA and EsxB proteins are founding members of the WXG100 (WXG) protein family, characterized by their small size (approximately 100 amino acids) and conserved WXG amino acid motif. M. tuberculosis contains 11 tandem pairs of WXG genes; each gene pair is thought to be coexpressed to form a heterodimer. The precise role of these proteins in the biology of M. tuberculosis is unknown, but several of the heterodimers are secreted, which is important for virulence. However, WXG proteins are not simply virulence factors, since nonpathogenic mycobacteria also express and secrete these proteins. Here we show that three WXG heterodimers have structures and properties similar to those of the M. tuberculosis EsxBA (MtbEsxBA) heterodimer, regardless of their host species and apparent biological function. Biophysical studies indicate that the WXG proteins from M. tuberculosis (EsxG and EsxH), Mycobacterium smegmatis (EsxA and EsxB), and Corynebacterium diphtheriae (EsxA and EsxB) are heterodimers and fold into a predominately alpha-helical structure. An in vivo protein-protein interaction assay was modified to identify proteins that interact specifically with the native WXG100 heterodimer. MtbEsxA and MtbEsxB were fused into a single polypeptide, MtbEsxBA, to create a biomimetic bait for the native heterodimer. The MtbEsxBA bait showed specific association with several esx-1-encoded proteins and EspA, a virulence protein secreted by ESX-1. The MtbEsxBA fusion peptide was also utilized to identify residues in both EsxA and EsxB that are important for establishing protein interactions with Rv3871 and EspA. Together, the results are consistent with a model in which WXG proteins perform similar biological roles in virulent and nonvirulent species.

Item Type:	Article
Uncontrolled Keywords:	amino acid sequence,bacterial proteins,circular dichroism,molecular sequence data,mutagenesis,mycobacterium,mycobacterium smegmatis,mycobacterium tuberculosis,protein binding,protein multimerization,sequence homology, amino acid,ultracentrifugation,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit
Depositing User:	Pure Connector
Date Deposited:	20 Jan 2014 16:04
Last Modified:	24 Oct 2022 05:34
URI:	https://ueaeprints.uea.ac.uk/id/eprint/46196
DOI:	10.1128/JB.01032-09

Actions (login required)

View Item