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Paralogous cAMP Receptor Proteins in Mycobacterium smegmatis Show Biochemical and Functional Divergence

Sharma, Ritu and Zaveri, Anisha and Gopalakrishnapai, Jayashree and Thiruneelakantan, Srinath and Thiruneelakantan, Umesh and Visweswariah, Sandhya S (2014) Paralogous cAMP Receptor Proteins in Mycobacterium smegmatis Show Biochemical and Functional Divergence. In: BIOCHEMISTRY, 53 (49). pp. 7765-7776.

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Official URL: http://dx.doi.org/ 10.1021/bi500924v


The cyclic AMP receptor protein (CRP) family of transcription factors consists of global regulators of bacterial gene expression. Here, we identify two paralogous CRPs in the genome of Mycobacterium smegmatis that have 78% identical sequences and characterize them biochemically and functionally. The two proteins (MSMEG_0539 and MSMEG_6189) show differences in cAMP binding affinity, trypsin sensitivity, and binding to a CRP site that we have identified upstream of the msmeg_3781 gene. MSMEG_6189 binds to the CRP site readily in the absence of cAMP, while MSMEG_0539 binds in the presence of cAMP, albeit weakly. msmeg_6189 appears to be an essential gene, while the ?msmeg_0539 strain was readily obtained. Using promoter-reporter constructs, we show that msmeg_3781 is regulated by CRP binding, and its transcription is repressed by MSMEG_6189. Our results are the first to characterize two paralogous and functional CRPs in a single bacterial genome. This gene duplication event has subsequently led to the evolution of two proteins whose biochemical differences translate to differential gene regulation, thus catering to the specific needs of the organism.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 06 Feb 2015 14:51
Last Modified: 06 Feb 2015 14:51
URI: http://eprints.iisc.ac.in/id/eprint/50780

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