Biophysical Journal 67: 105-112 (1994)
© 1994 the Biophysical Society

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sankaram, M B Search for Related Content PubMed PubMed Citation Articles by Sankaram, M B

Membrane interaction of small N-myristoylated peptides: implications for membrane anchoring and protein-protein association.

Department of Biochemistry, University of Virginia Health Sciences Center, Charlottesville 22908.

ABSTRACT

The effect of the covalent attachment of a myristolyl moiety to the N-terminal glycine residue in proteins, N-myristoylation, on lipid-protein interactions was investigated in a model system using magnetic resonance spectroscopic methods. Two peptides with sequences conserved among known N-myristoylated proteins were chosen for this study. Using two-dimensional nuclear magnetic resonance techniques, it was shown that N-myristolylation results in an aggregation of both peptides in solution, although they lack well defined folded conformations in solution either when chemically N-myristolyated or when nonacylated. The interaction of the acylated peptides with lipid bilayers was investigated using spin label electron spin resonance and 2H NMR techniques. The results show that when bound to membranes, the covalently linked myristoyl chain of one of the peptides is directly inserted into or anchored to the lipid bilayer. The binding of the other peptide with membranes is effected by interactions between amino acid residues and the phospholipid headgroups. In this case, the covalently linked myristoyl moiety is most likely not in direct contact with the acyl chains of the host lipid bilayer. Rather, the N-myristoyl chains stabilize the peptide aggregate by forming a hydrophobic core. Measurements of peptide binding to membranes showed that N-myristoylation affects both the lipid:peptide stoichiometry at saturation and the equilibrium binding constant, in a manner that is consistent with the structural information obtained by magnetic resonance methods.

This article has been cited by other articles:

				T. Adachi, S. Stafford, S. Sur, and R. Alam A Novel Lyn-Binding Peptide Inhibitor Blocks Eosinophil Differentiation, Survival, and Airway Eosinophilic Inflammation1, 2 J. Immunol., July 15, 1999; 163(2): 939 - 946. [Abstract] [Full Text] [PDF]

				T. Adachi, K. Pazdrak, S. Stafford, and R. Alam The Mapping of the Lyn Kinase Binding Site of the Common {beta} Subunit of IL-3/Granulocyte-Macrophage Colony- Stimulating Factor/IL-5 Receptor J. Immunol., February 1, 1999; 162(3): 1496 - 1501. [Abstract] [Full Text] [PDF]

				E. Leal-Pinto, W. Tao, J. Rappaport, M. Richardson, B. A. Knorr, and R. G. Abramson Molecular Cloning and Functional Reconstitution of a Urate Transporter/Channel J. Biol. Chem., January 3, 1997; 272(1): 617 - 625. [Abstract] [Full Text] [PDF]

				O. Vinogradova, T. Haas, E. F. Plow, and J. Qin A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit PNAS, February 15, 2000; 97(4): 1450 - 1455. [Abstract] [Full Text] [PDF]