5YC1

TRAF4_GPIb complex

Summary for 5YC1

• Entry DOI: 10.2210/pdb5yc1/pdb
• Descriptor: TNF receptor-associated factor 4, GPIb peptide (3 entities in total)
• Functional Keywords: complex, platelet receptor, traf4, interaction, signaling protein-peptide complex, signaling protein/peptide
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: Q9BUZ4
• Total number of polymer chains: 9
• Total formula weight: 126295.93

Authors

Park, H.H.,Kim, C.M. (deposition date: 2017-09-06, release date: 2017-10-11, Last modification date: 2024-03-27)

Primary citation

Kim, C.M.,Son, Y.J.,Kim, S.,Kim, S.Y.,Park, H.H.
Molecular basis for unique specificity of human TRAF4 for platelets GPIb beta and GPVI
Proc. Natl. Acad. Sci. U.S.A., 114:11422-11427, 2017

PubMed Abstract: Tumor necrosis factor (TNF)-receptor associated factor 4 (TRAF4), an adaptor protein with E3-ligase activity, is involved in embryogenesis, cancer initiation and progression, and platelet receptor (GPIb-IX-V complex and GPVI)-mediated signaling for reactive oxygen species (ROS) production that initiates thrombosis at arterial shears. Disruption of platelet receptors and the TRAF4 interaction is a potential target for therapeutic intervention by antithrombotic drugs. Here, we report a crystal structure of TRAF4 (amino acid residues 290∼470) in complex with a peptide from the GPIbβ receptor (amino acid residues 177∼181). The GPIbβ peptide binds to a unique shallow surface composed of two hydrophobic pockets on TRAF4. Further studies revealed the TRAF4-binding motif Arg-Leu-X-Ala. The TRAF4-binding motif was present not only in platelet receptors but also in the TGF-β receptor. The current structure will provide a template for furthering our understanding of the receptor-binding specificity of TRAF4, TRAF4-mediated signaling, and related diseases.

PubMed: 29073066
DOI: 10.1073/pnas.1708688114

Experimental method

X-RAY DIFFRACTION (2.506 Å)