Toggling of Diacylglycerol Affinity Correlates with Conformational Plasticity in C1 Domains. Academic Article

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.

authors

• Igumenova, Tatyana

published proceedings

• Biochemistry

author list (cited authors)

• Stewart, M. D., & Igumenova, T. I.

citation count

• 7

complete list of authors

• Stewart, Mikaela D||Igumenova, Tatyana I

publication date

• May 2017

publisher

• American Chemical Society (ACS)  Publisher

published in

• Biochemistry  Journal

keywords

• Diglycerides
• Models, Molecular
• Protein Conformation
• Protein Kinase C
• Thermodynamics

PubMed Central ID

• 28505428

Digital Object Identifier (DOI)

• 10.1021/acs.biochem.7b00228

start page

• 2637

end page

• 2640

volume

• 56

issue

• 21

URL

• http%3A%2F%2Fdx.doi.org%2F10.1021%2Facs.biochem.7b00228