Membrane Binding of Myristylated Peptides Corresponding to the NH2 Terminus of Src
| Autor: | Marilyn D. Resh, Carolyn A. Buser, Stuart McLaughlin, Catherine T. Sigal |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Gene Expression Regulation
Viral Models Molecular Stereochemistry Recombinant Fusion Proteins Lipid Bilayers Molecular Sequence Data Lysine Coated Vesicles Peptide Biochemistry Oncogene Protein pp60(v-src) chemistry.chemical_compound Phosphatidylcholine Amino Acid Sequence Amino Acids chemistry.chemical_classification Rous sarcoma virus Myristates biology Vesicle Biological membrane biology.organism_classification Membrane Avian Sarcoma Viruses chemistry Isotope Labeling Electrophoresis Polyacrylamide Gel Protein Binding Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biochemistry. 33:13093-13101 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi00248a019 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|