TY  - JOUR
AU  - Bauer, F.
AU  - Schweimer, K.
AU  - Meiselbach, H.
AU  - Hoffmann, S.
AU  - Rosch, P.
AU  - Sticht, H.
TI  - Structural characterization of Lyn-SH3 domain in complex with a herpesviral protein reveals an extended recognition motif that enhances binding affinity
JO  - Protein science
VL  - 14
SN  - 0961-8368
CY  - Hoboken, NJ
PB  - Wiley
M1  - PreJuSER-49418
SP  - 2487 -2498
PY  - 2005
N1  - Record converted from VDB: 12.11.2012
AB  - The Src homology 3 (SH3) domain of the Src family kinase Lyn binds to the herpesviral tyrosine kinase interacting protein (Tip) more than one order of magnitude stronger than other closely related members of the Src family. In order to identify the molecular basis for high-affinity binding, the structure of free and Tip-bound Lyn-SH3 was determined by NMR spectroscopy. Tip forms additional contacts outside its classical proline-rich recognition motif and, in particular, a strictly conserved leucine (L186) of the C-terminally adjacent sequence stretch packs into a hydrophobic pocket on the Lyn surface. Although the existence of this pocket is no unique property of Lyn-SH3, Lyn is the only Src family kinase that contains an additional aromatic residue (H41) in the n-Src loop as part of this pocket. H41 covers L186 of Tip by forming tight hydrophobic contacts, and model calculations suggest that the increase in binding affinity compared with other SH3 domains can mainly be attributed to these additional interactions. These findings indicate that this pocket can mediate specificity even between otherwise closely related SH3 domains.
KW  - Models, Molecular
KW  - Multiprotein Complexes: chemistry
KW  - Multiprotein Complexes: metabolism
KW  - Nuclear Magnetic Resonance, Biomolecular: methods
KW  - Phosphoproteins: chemistry
KW  - Phosphoproteins: metabolism
KW  - Protein Binding
KW  - Protein Structure, Quaternary
KW  - Viral Proteins: chemistry
KW  - Viral Proteins: metabolism
KW  - src Homology Domains
KW  - src-Family Kinases: chemistry
KW  - src-Family Kinases: metabolism
KW  - Multiprotein Complexes (NLM Chemicals)
KW  - Phosphoproteins (NLM Chemicals)
KW  - Viral Proteins (NLM Chemicals)
KW  - tyrosine kinase interacting protein, Saimiriine herpesvirus 2 (NLM Chemicals)
KW  - lyn protein-tyrosine kinase (NLM Chemicals)
KW  - src-Family Kinases (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:16155203
C2  - pmc:PMC2253286
UR  - <Go to ISI:>//WOS:000232233400001
DO  - DOI:10.1110/ps.051563605
UR  - https://juser.fz-juelich.de/record/49418
ER  -