Abstract
AbstractGlutamine synthetases (GS) play central roles in cellular nitrogen assimilation. Although GS active-site formation requires the oligomerization of just two GS subunits, all GS form large, multi-oligomeric machines. Here we describe a structural dissection of the archaeal Methanosarcina mazei (Mm) GS and its regulation. We show that Mm GS forms unstable dodecamers. Strikingly, we show this Mm GS oligomerization property is leveraged for a unique mode of regulation whereby labile Mm GS hexamers are stabilized by binding the nitrogen regulatory protein, GlnK1. Our GS-GlnK1 structure shows that GlnK1 functions as molecular glue to affix GS hexamers together, stabilizing formation of GS active-sites. These data, therefore, reveal the structural basis for a unique form of enzyme regulation by oligomer modulation.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference50 articles.
1. Eisenberg, D., Gill, H. S., Pfluegl, G. M. & Rotstein, S. H. Structure-function relationships of glutamine synthetases. Biochim Biophys. Acta 1477, 122–145 (2000).
2. Purich, D. L. Advances in the enzymology of glutamine synthesis. Adv. Enzymol. Relat. Areas Mol. Biol. 72, 9–42 (1998).
3. Schumacher, J. et al. Nitrogen and carbon status are integrated at the transcriptional level by the nitrogen regulator NtrC in vivo. mBio 19, e00881–13 (2013).
4. Kumada, Y. et al. Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes. Proc. Natl Acad. Sci. USA 90, 3009–3013 (1993).
5. Brown J. R., Masuchi Y., Robb F. T., Doolittle W. F. 1994. Evolutionary relationships of bacterial and archaeal glutamine synthetase genes. J. Mol. Evol. 38: 566–576.
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