Enriching the annotation of Mycobacterium tuberculosis H37Rv proteome using remote homology detection approaches: Insights into structure and function

Ramakrishnan, Gayatri and Ochoa-Montano, Bernardo and Raghavender, Upadhyayula S and Mudgal, Richa and Joshi, Adwait G and Chandra, Nagasuma R and Sowdhamini, Ramanathan and Blundell, Tom L and Srinivasan, Narayanaswamy (2015) Enriching the annotation of Mycobacterium tuberculosis H37Rv proteome using remote homology detection approaches: Insights into structure and function. In: TUBERCULOSIS, 95 (1). pp. 14-25.

PDF tub_95-1_14_2015.pdf - Published Version Restricted to Registered users only Download (2MB) | Request a copy

Abstract

The availability of the genome sequence of Mycobacterium tuberculosis H37Rv has encouraged determination of large numbers of protein structures and detailed definition of the biological information encoded therein; yet, the functions of many proteins in M. tuberculosis remain unknown. The emergence of multidrug resistant strains makes it a priority to exploit recent advances in homology recognition and structure prediction to re-analyse its gene products. Here we report the structural and functional characterization of gene products encoded in the M. tuberculosis genome, with the help of sensitive profile-based remote homology search and fold recognition algorithms resulting in an enhanced annotation of the proteome where 95% of the M. tuberculosis proteins were identified wholly or partly with information on structure or function. New information includes association of 244 proteins with 205 domain families and a separate set of new association of folds to 64 proteins. Extending structural information across uncharacterized protein families represented in the M. tuberculosis proteome, by determining superfamily relationships between families of known and unknown structures, has contributed to an enhancement in the knowledge of structural content. In retrospect, such superfamily relationships have facilitated recognition of probable structure and/or function for several uncharacterized protein families, eventually aiding recognition of probable functions for homologous proteins corresponding to such families. Gene products unique to mycobacteria for which no functions could be identified are 183. Of these 18 were determined to be M. tuberculosis specific. Such pathogen-specific proteins are speculated to harbour virulence factors required for pathogenesis. A re-annotated proteome of M. tuberculosis, with greater completeness of annotated proteins and domain assigned regions, provides a valuable basis for experimental endeavours designed to obtain a better understanding of pathogenesis and to accelerate the process of drug target discovery. (C) 2014 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Publication:	TUBERCULOSIS
Publisher:	CHURCHILL LIVINGSTONE
Additional Information:	Copyright for this article belongs to the CHURCHILL LIVINGSTONE, JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
Keywords:	Mycobacterium tuberculosis; Protein annotation; Remote homology detection; Sequence analysis
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	28 Jan 2015 04:28
Last Modified:	28 Jan 2015 04:28
URI:	http://eprints.iisc.ac.in/id/eprint/50750

Actions (login required)

View Item