title: Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain.
abstract: The three-dimensional structure of the N-terminal SH3 domain (residues 583-660) of murine Vav, which contains a tetra-proline sequence (Pro 607-Pro 610), was determined by NMR. The solution structure of the SH3 domain shows a typical SH3 fold, but it exists in two conformations due to cis-trans isomerization at the Gly614-Pro615 bond. The NMR structure of the P615G mutant, where Pro615 is replaced by glycine, reveals that the tetra-proline region is inserted into the RT-loop and binds to its own SH3 structure. The C-terminal SH3 domain of Grb2 specifically binds to the trans form of the N-terminal SH3 domain of Vav. The surface of Vav N-terminal SH3 which binds to Grb2 C-terminal SH3 was elucidated by chemical shift mapping experiments using NMR. The surface does not involve the tetra-proline region but involves the region comprising the n-src loop, the N-terminal and the C-terminal regions. This surface is located opposite to the tetra-proline containing region, consistent with that of our previous mutagenesis studies.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogura
authors.forename: Koji
authors.initials: K
authors.lastname: Nagata
authors.forename: Masataka
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Etsuko
authors.initials: E
authors.lastname: Ebisui
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Hasuda
authors.forename: Satoru
authors.initials: S
authors.lastname: Yuzawa
authors.forename: Motohiko
authors.initials: M
authors.lastname: Nishida
authors.forename: Hideki
authors.initials: H
authors.lastname: Hatanaka
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Inagaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D051380:GRB2 Adaptor Protein; D007536:Isomerism; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D012996:Solutions; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D012996:Solutions; C496619:Vav1 protein, mouse