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Biophys. J. BioFAST: First Published June 8, 2007. doi:10.1529/biophysj.107.109967
© 2007 by the Biophysical Society.

A more recent version of this article appeared on October 1, 2007.
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Yana K. Reshetnyak
Oleg A Andreev
Donald M Engelman
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MEMBRANES

A monomeric membrane peptide that lives in three worlds: in solution, attached to and inserted across lipid bilayers

Yana K. Reshetnyak 1*, Michael Segala 1, Oleg A Andreev 1 and Donald M Engelman 2

1 Physics Department, University of Rhode Island
2 Yale University, Department of Molecular Biophysics and Biochemistry

* To whom correspondence should be addressed. E-mail: reshetnyak{at}mail.uri.edu.

Submitted on March 30, 2007
Revised on May 18, 2007
Accepted on 1 June 2007


  Abstract
The membrane peptide pHLIP (pH (Low) Insertion Peptide) lives in three worlds, being soluble in aqueous solution at pH 7.4, binding to the surface of lipid bilayers, and inserting as a transbilayer helix at low pH. With low pH driving the process, pHLIP can translocate cargo molecules attached to its C-terminus via a disulfide and release them in the cytoplasm of a cell. Here we examine a key aspect of the mechanism, showing that pHLIP is monomeric in each of its three major states: soluble in water near neutral pH (state I), bound to the surface of a membrane near neutral pH (state II), and inserted across the membrane as an {alpha}-helix at low pH (state III). The peptide does not induce fusion or membrane leakage. The unique properties of pHLIP made it attractive for the biophysical investigation of membrane protein folding in vitro and for the development of a novel class of delivery peptides for the transport of therapeutic and diagnostic agents to acidic tissue sites associated with various pathological processes in vivo.

Key Words: fluorescence, membrane peptide, pH-dependent membrane insertion, pHLIP pH Low Insertion Peptide




This article has been cited by other articles:


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 Proc. Natl. Acad. Sci. USAHome page
Y. K. Reshetnyak, O. A. Andreev, M. Segala, V. S. Markin, and D. M. Engelman
Energetics of peptide (pHLIP) binding to and folding across a lipid bilayer membrane
PNAS, October 7, 2008; 105(40): 15340 - 15345.
[Abstract] [Full Text] [PDF]

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 Biophys. JHome page
M. Zoonens, Y. K. Reshetnyak, and D. M. Engelman
Bilayer Interactions of pHLIP, a Peptide that Can Deliver Drugs and Target Tumors
Biophys. J., July 1, 2008; 95(1): 225 - 235.
[Abstract] [Full Text] [PDF]


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Copyright © 2007 by the Biophysical Society.