Toggling of Diacylglycerol Affinity Correlates with Conformational Plasticity in C1 Domains

Biochemistry
Mikaela D Stewart, Tatyana I Igumenova

Abstract

Conserved homology-1 (C1) domains are peripheral membrane domains that target their host proteins to diacylglycerol (DAG)-containing membranes. It has been previously shown that a conservative aromatic mutation of a single residue in the C1 domain has a profound effect on DAG affinity. We report that the "DAG-toggling" mutation changes the conformational dynamics of the loop region that forms the binding site for the C1 activators. Moreover, there is a correlation among the residue identity at the mutation site, DAG affinity, and loop dynamics in four C1 variants. We propose that "toggling" of DAG affinity may occur through modulation of both protein-membrane interactions and the geometry of the activator-binding cleft, with the loop dynamics being responsible for the latter.

References

Feb 1, 1997·Protein Science : a Publication of the Protein Society·J H HurleyY Nishizuka
Jun 15, 2004·Current Opinion in Neurobiology·Nils BroseHeike Wegmeyer
Oct 31, 2006·The Journal of Biological Chemistry·Daniel R DriesAlexandra C Newton
Dec 13, 2006·Trends in Biochemical Sciences·Silvia Carrasco, Isabel Mérida
Aug 23, 2008·IUBMB Life·Lisa L Gallegos, Alexandra C Newton
Nov 13, 2008·The Journal of Biological Chemistry·Yongmei PuPeter M Blumberg
Mar 3, 2010·Journal of Biomolecular NMR·Veniamin ChevelkovNikolai R Skrynnikov
Mar 23, 2011·Journal of Molecular Biology·Mikaela D StewartTatyana I Igumenova
May 1, 2012·Protein Science : a Publication of the Protein Society·John J SkinnerS Walter Englander
May 1, 2012·Protein Science : a Publication of the Protein Society·John J SkinnerS Walter Englander
Aug 24, 2012·Biochemistry·Mikaela D Stewart, Tatyana I Igumenova
Jul 31, 2014·Journal of the American Chemical Society·Jianing LiGregory A Voth
Aug 16, 2014·The Journal of Biological Chemistry·Mikaela D StewartTatyana I Igumenova

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Citations

Mar 8, 2018·Critical Reviews in Biochemistry and Molecular Biology·Alexandra C Newton
Feb 3, 2021·Advances in Biological Regulation·Sachin Katti, Tatyana I Igumenova
Apr 6, 2021·Biochemistry·Youngki YouJoydip Das
Nov 16, 2021·Journal of Biomolecular Structure & Dynamics·Youngki You, Joydip Das

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