Membrane binding of myristylated peptides corresponding to the NH2 terminus of Src

Biochemistry. 1994 Nov 8;33(44):13093-101. doi: 10.1021/bi00248a019.


Membrane association is required for cell transformation by pp60v-src (v-Src), the product of the v-src oncogene of Rous sarcoma virus. Previous experiments have identified two NH2-terminal membrane-binding motifs: a myristate (14-carbon acyl chain) attached to the NH2-terminal glycine and three basic residues at positions 5, 7, and 9 of Src. We examined the membrane binding of each motif using myristylated (myr-src) and nonmyristylated (nonmyr-src) peptides corresponding to the NH2 terminus of Src. All myristylated peptides partitioned equally well onto electrically neutral phosphatidylcholine vesicles (K1 = 10(4) M-1). Identical binding has been observed for simple myristylated peptides (e.g., myr-Gly) and arises from the hydrophobic insertion of the myristate into the bilayer. A nonmyristylated peptide corresponding to residues 2-16 of Src [nonmyr-src(2-16), net charge = +5] bound to vesicles containing 33% monovalent acidic phospholipids with K1 = 10(3) M-1. Penta(lysine) (+5 net charge) exhibits the same binding behavior, which is due to the electrostatic interaction between basic residues and acidic lipids. The corresponding myristylated peptide, myr-src(2-16), binds 3 orders of magnitude more strongly to vesicles containing 33% acidic lipids than to neutral vesicles. The resulting apparent association constant, K1 = 10(7) M-1, is approximately equal to the product of the partition coefficients for the two individual interactions. This 10(7) M-1 binding is sufficiently strong to anchor the Src protein to biological membranes. We propose a simple model that explains the observed synergism between the two peptide-membrane interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / metabolism
  • Avian Sarcoma Viruses / genetics*
  • Coated Vesicles
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Regulation, Viral / genetics
  • Isotope Labeling
  • Lipid Bilayers / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Myristates / chemistry*
  • Myristates / metabolism
  • Oncogene Protein pp60(v-src) / chemistry
  • Oncogene Protein pp60(v-src) / genetics*
  • Oncogene Protein pp60(v-src) / metabolism
  • Protein Binding
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics


  • Amino Acids
  • Lipid Bilayers
  • Myristates
  • Recombinant Fusion Proteins
  • Oncogene Protein pp60(v-src)