A Universal Stress Protein (USP) in Mycobacteria Binds cAMP

Banerjee, Arka and Adolph, Ramona S and Gopalakrishnapai, Jayashree and Kleinboelting, Silke and Emmerich, Christiane and Steegborn, Clemens and Visweswariah, Sandhya S (2015) A Universal Stress Protein (USP) in Mycobacteria Binds cAMP. In: JOURNAL OF BIOLOGICAL CHEMISTRY, 290 (20). pp. 12731-12743.

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Abstract

Mycobacteria are endowed with rich and diverse machinery for the synthesis, utilization, and degradation of cAMP. The actions of cyclic nucleotides are generally mediated by binding of cAMP to conserved and well characterized cyclic nucleotide binding domains or structurally distinct cGMP-specific and -regulated cyclic nucleotide phosphodiesterase, adenylyl cyclase, and E. coli transcription factor FhlA (GAF) domain-containing proteins. Proteins with cyclic nucleotide binding and GAF domains can be identified in the genome of mycobacterial species, and some of them have been characterized. Here, we show that a significant fraction of intracellular cAMP is bound to protein in mycobacterial species, and by using affinity chromatography techniques, we identify specific universal stress proteins (USP) as abundantly expressed cAMP-binding proteins in slow growing as well as fast growing mycobacteria. We have characterized the biochemical and thermodynamic parameters for binding of cAMP, and we show that these USPs bind cAMP with a higher affinity than ATP, an established ligand for other USPs. We determined the structure of the USP MSMEG_3811 bound to cAMP, and we confirmed through structure-guided mutagenesis, the residues important for cAMP binding. This family of USPs is conserved in all mycobacteria, and we suggest that they serve as ``sinks'' for cAMP, making this second messenger available for downstream effectors as and when ATP levels are altered in the cell.

Item Type:	Journal Article
Publication:	JOURNAL OF BIOLOGICAL CHEMISTRY
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Additional Information:	Copy right for this article belongs to the AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	22 Jun 2015 05:32
Last Modified:	22 Jun 2015 05:32
URI:	http://eprints.iisc.ac.in/id/eprint/51726

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