title: Fatty acyl chain-dependent but charge-independent association of the SH4 domain of Lck with lipid membranes.
abstract: The SH4 domain of Src family of nonreceptor protein tyrosine kinases represents the extreme N-terminal 1-16 amino acid region which mediates membrane association of these proteins and facilitates their functions. The SH4 domains among Src members lack well-defined sequence consensus and vary in the net charge. However, they readily anchor to the cytoplasmic face of the plasma membrane upon fatty acid acylation. Here, we report the membrane association of differentially acylated SH4 domain of Lck kinase, which has net negative charge at physiological pH. Our results suggest that despite the net negative charge, the SH4 domain of Lck associates with membranes upon fatty acid acylation. While myristoylation at the N-terminus is sufficient for providing membrane anchorage, multiple acylation determines orientation of the peptide chain with respect to the lipid bilayer. Hence, fatty acylation serves more than just a lipid anchor. It has an important role in regulating the spatial orientation of the peptide domain with respect to the lipid bilayer, which could be important for the interaction of the other domains of these kinases with their partners.
authors: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India.
authors: Anoop
authors: A
authors: Rawat
authors: Avaronnan
authors: A
authors: Harishchandran
authors: Ramakrishnan
authors: R
authors: Nagaraj
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D001665:Binding Sites; D005227:Fatty Acids / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D019814:Myristic Acid / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D060327:Solid-Phase Synthesis Techniques; D055672:Static Electricity; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D005227:Fatty Acids; D008563:Membrane Lipids; D010455:Peptides; D053835:Unilamellar Liposomes; D019814:Myristic Acid; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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