Structure of a helically extended SH3 domain of the T cell adapter protein ADAP.
The adapter protein ADAP (FYB/SLAP-130) provides a critical link between T cell receptor (TCR) signaling and cell adhesion via the activation of integrins. The C-terminal 70 residues of ADAP show homology to SH3 domains; however, conserved residues of the fold are absent. An alignment and annotation of this domain has therefore been elusive. We have solved the three-dimensional structure of the ADAP C-terminal domain by NMR spectroscopy and show that it represents an altered SH3 domain fold. An N-terminal, amphipathic helix makes extensive contacts to residues of the regular SH3 domain fold, and thereby a composite surface with unusual surface properties is created. We propose this SH3 domain variant to be classified as a helically extended SH3 domain (hSH3 domain) and show that the ADAP-hSH3 domain can no longer bind conventional proline-rich peptides.
Heuer
Katja
K
Protein Engineering Group, Forschungsinstitut für Molekulare Pharmakologie and Freie Universität Berlin, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Kofler
Michael
M
Langdon
Grant
G
Thiemke
Katharina
K
Freund
Christian
C
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C106957:FYB1 protein, human