Mycobacterium tuberculosis RsdA provides a conformational rationale for selective regulation of sigma-factor activity by proteolysis

Jaiswal, Ravi K and Prabha, Tangirala Surya and Manjeera, Gowravaram and Gopal, Balasubramanian (2013) Mycobacterium tuberculosis RsdA provides a conformational rationale for selective regulation of sigma-factor activity by proteolysis. In: Nucleic Acids Research, 41 (5). pp. 3414-3423.

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Abstract

The relative levels of different sigma factors dictate the expression profile of a bacterium. Extracytoplasmic function sigma factors synchronize the transcriptional profile with environmental conditions. The cellular concentration of free extracytoplasmic function sigma factors is regulated by the localization of this protein in a sigma/anti-sigma complex. Anti-sigma factors are multi-domain proteins with a receptor to sense environmental stimuli and a conserved anti-sigma domain (ASD) that binds a sigma factor. Here we describe the structure of Mycobacterium tuberculosis anti-sigma(D) (RsdA) in complex with the -35 promoter binding domain of sigma(D) (sigma(D)(4)). We note distinct conformational features that enable the release of sigma(D) by the selective proteolysis of the ASD in RsdA. The structural and biochemical features of the sigma(D)/RsdA complex provide a basis to reconcile diverse regulatory mechanisms that govern sigma/anti-sigma interactions despite high overall structural similarity. Multiple regulatory mechanisms embedded in an ASD scaffold thus provide an elegant route to rapidly re-engineer the expression profile of a bacterium in response to an environmental stimulus.

Item Type:	Journal Article
Publication:	Nucleic Acids Research
Publisher:	Oxford University Press
Additional Information:	Copyright of this article belongs to Oxford University Press .
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	10 Jun 2013 07:35
Last Modified:	10 Jun 2013 07:35
URI:	http://eprints.iisc.ac.in/id/eprint/46661

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