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Interfacial Polar Interactions Affect Gramicidin Channel Kinetics

Tatiana K. Rostovtseva ^*, Horia I. Petrache , Namdar Kazemi ^*, Elnaz Hassanzadeh ^* and Sergey M. Bezrukov ^*

^* Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; and Department of Physics, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202

Correspondence: Address reprint requests and inquiries to Tatiana K. Rostovtseva, Tel.: 301-402-4702; Fax: 301-496-2172; E-mail: rostovtt{at}mail.nih.gov.

Critical to biological processes such as secretion and transport, protein-lipid interactions within the membrane and at the membrane-water interface still raise many questions. Here we examine the role of lipid headgroups in these interactions by using gramicidin A (gA) channels in planar bilayers as a probe. We show that although headgroup demethylation from phosphatidylcholine (DOPC) to phosphatidylethanolamine decreases the lifetime of gA channels by an order of magnitude in accordance with the currently accepted hydrophobic mismatch mechanism, our findings with diether-DOPC suggest the importance of the headgroup-peptide interactions. According to our x-ray diffraction measurements, this lipid has the same hydrophobic thickness as DOPC but increases gA lifetime by a factor of 2. Thus we demonstrate that peptide-headgroup interactions may dominate over the effect of hydrophobic mismatch in regulating protein function.