The structural basis for the recognition of diverse receptor sequences by TRAF2.
Many members of the tumor necrosis factor receptor (TNFR) superfamily initiate intracellular signaling by recruiting TNFR-associated factors (TRAFs) through their cytoplasmic tails. TRAFs apparently recognize highly diverse receptor sequences. Crystal structures of the TRAF domain of human TRAF2 in complex with peptides from the TNFR family members CD40, CD30, Ox40, 4-1BB, and the EBV oncoprotein LMP1 revealed a conserved binding mode. A major TRAF2-binding consensus sequence, (P/S/A/T)x(Q/E)E, and a minor consensus motif, PxQxxD, can be defined from the structural analysis, which encompass all known TRAF2-binding sequences. The structural information provides a template for the further dissection of receptor binding specificity of TRAF2 and for the understanding of the complexity of TRAF-mediated signal transduction.
Ye
H
H
Department of Biochemistry, Weill Medical College, New York, New York, USA.
Park
Y C
YC
Kreishman
M
M
Kieff
E
E
Wu
H
H
D000595:Amino Acid Sequence; D015703:Antigens, CD; D001665:Binding Sites; D019013:CD40 Antigens / Q000737:chemistry / Q000378:metabolism; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D017730:Ki-1 Antigen / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000378:metabolism
D015703:Antigens, CD; D019013:CD40 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D017730:Ki-1 Antigen; D010446:Peptide Fragments; D011506:Proteins; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D047992:TNF Receptor-Associated Factor 2; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D014763:Viral Matrix Proteins