Unraveling Allostery in a Knotted Minimal Methyltransferase by NMR Spectroscopy

Journal of Molecular Biology
Dominique T CapraroPatricia A Jennings

Abstract

The methyltransferases that belong to the SpoU-TrmD family contain trefoil knots in their backbone fold. Recent structural dynamic and binding analyses of both free and bound homologs indicate that the knot within the polypeptide backbone plays a significant role in the biological activity of the molecule. The knot loops form the S-adenosyl-methionine (SAM)-binding pocket as well as participate in SAM binding and catalysis. Knots contain both at once a stable core as well as moving parts that modulate long-range motions. Here, we sought to understand allosteric effects modulated by the knotted topology. Uncovering the residues that contribute to these changes and the functional aspects of these protein motions are essential to understanding the interplay between the knot, activation of the methyltransferase, and the implications in RNA interactions. The question we sought to address is as follows: How does the knot, which constricts the backbone as well as forms the SAM-binding pocket with its three distinctive loops, affect the binding mechanism? Using a minimally tied trefoil protein as the framework for understanding the structure-function roles, we offer an unprecedented view of the conformational mechanics of the knot and ...Continue Reading

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Dec 10, 1998·Nucleic Acids Research·J RozenskiJ A McCloskey
Jun 26, 2002·Biochemistry·Gordon G Hammes
Dec 31, 2002·Current Opinion in Structural Biology·Jennifer L Martin, Fiona M McMillan
Jun 27, 2003·Trends in Biochemical Sciences·Heidi L SchubertXiaodong Cheng
Mar 7, 2007·BMC Bioinformatics·Karolina L TkaczukJanusz M Bujnicki
Oct 24, 2007·Journal of Biomolecular NMR·Frank H SchumannHans Robert Kalbitzer
Jul 2, 2009·Protein Science : a Publication of the Protein Society·Benjamin J Cole, Christopher Bystroff
Mar 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Rajeevan SelvaratnamGiuseppe Melacini
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Dominique T CapraroPatricia A Jennings
Jun 14, 2012·PloS One·Dominique T CapraroPatricia A Jennings
Aug 22, 2013·Progress in Nuclear Magnetic Resonance Spectroscopy·Mike P Williamson
Dec 17, 2014·Bioinformatics·Woonghee LeeJohn L Markley
Aug 21, 2015·Journal of Physics. Condensed Matter : an Institute of Physics Journal·David J BurbanPatricia A Jennings
Jan 7, 2016·Chemical Reviews·George P Lisi, J Patrick Loria
Mar 10, 2016·Biophysical Journal·Dominique T Capraro, Patricia A Jennings
Aug 30, 2016·Nature Structural & Molecular Biology·Thomas ChristianYa-Ming Hou

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