Structural recognition mechanisms between human Src homology domain 3 (SH3) and ALG-2-interacting protein X (Alix).
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.
CNRS UMR 7258, INSERM U 1068, Centre de Recherche en Cancérologie de Marseille, Marseille F-13009, France.
Xiaoli
X
Shi
Stephane
S
Betzi
Adrien
A
Lugari
Sandrine
S
Opi
Audrey
A
Restouin
Isabelle
I
Parrot
Jean
J
Martinez
Pascale
P
Zimmermann
Patrick
P
Lecine
Mingdong
M
Huang
Stefan T
ST
Arold
Yves
Y
Collette
Xavier
X
Morelli
D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D051572:Proto-Oncogene Proteins c-hck / Q000737:chemistry* / Q000378:metabolism; D053838:Scattering, Small Angle; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C117020:PDCD6IP protein, human; D054311:nef Gene Products, Human Immunodeficiency Virus; D011392:Proline; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck