Abstract
The functions of Src family kinases are tightly regulated through Src homology (SH) domain-mediated protein-protein interactions. We previously reported the biophysical characteristics of the apoptosis-linked gene 2-interacting protein X (Alix) in complex with the haemopoietic cell kinase (Hck) SH3 domain. In the current study, we have combined ITC, NMR, SAXS and molecular modeling to determine a 3D model of the complex. We demonstrate that Hck SH3 recognizes an extended linear proline-rich region of Alix. This particular binding mode enables Hck SH3 to sense a specific non-canonical residue situated in the SH3 RT-loop of the kinase. The resulting model helps clarify the mechanistic insights of Alix-Hck interaction.
Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Binding Sites
-
Calcium-Binding Proteins / chemistry*
-
Calcium-Binding Proteins / metabolism
-
Cell Cycle Proteins / chemistry*
-
Cell Cycle Proteins / metabolism
-
Endosomal Sorting Complexes Required for Transport / chemistry*
-
Endosomal Sorting Complexes Required for Transport / metabolism
-
Humans
-
Models, Molecular
-
Nuclear Magnetic Resonance, Biomolecular
-
Proline / genetics
-
Proline / metabolism
-
Protein Conformation
-
Proto-Oncogene Proteins c-hck / chemistry*
-
Proto-Oncogene Proteins c-hck / metabolism
-
Scattering, Small Angle
-
nef Gene Products, Human Immunodeficiency Virus / chemistry
-
nef Gene Products, Human Immunodeficiency Virus / metabolism
-
src Homology Domains*
Substances
-
Calcium-Binding Proteins
-
Cell Cycle Proteins
-
Endosomal Sorting Complexes Required for Transport
-
PDCD6IP protein, human
-
nef Gene Products, Human Immunodeficiency Virus
-
Proline
-
HCK protein, human
-
Proto-Oncogene Proteins c-hck