Unexpected functional implication of a stable succinimide in the structural stability of Methanocaldococcus jannaschii glutaminase

Kumar, Sanjeev and Prakash, Sunita and Gupta, Kallol and Dongre, Aparna and Balaram, Padmanabhan and Balaram, Hemalatha (2016) Unexpected functional implication of a stable succinimide in the structural stability of Methanocaldococcus jannaschii glutaminase. In: NATURE COMMUNICATIONS, 7 .

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Abstract

Protein ageing is often mediated by the formation of succinimide intermediates. These short-lived intermediates derive from asparaginyl deamidation and aspartyl dehydration and are rapidly converted into beta-aspartyl or D-aspartyl residues. Here we report the presence of a highly stable succinimide intermediate in the glutaminase subunit of GMP synthetase from the hyperthermophile Methanocaldoccocus jannaschii. By comparing the biophysical properties of the wild-type protein and of several mutants, we show that the presence of succinimide increases the structural stability of the glutaminase subunit. The protein bearing this modification in fact remains folded at 100 degrees C and in 8M guanidinium chloride. Mutation of the residue following the reactive asparagine provides insight into the factors that contribute to the hydrolytic stability of the succinimide. Our findings suggest that sequences that stabilize succinimides from hydrolysis may be evolutionarily selected to confer extreme thermal stability.

Item Type:	Journal Article
Publication:	NATURE COMMUNICATIONS
Additional Information:	Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	03 Dec 2016 09:30
Last Modified:	03 Dec 2016 09:30
URI:	http://eprints.iisc.ac.in/id/eprint/55357

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