Molecular basis for TANK recognition by TRAF1 revealed by the crystal structure of TRAF1/TANK complex.
Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a multifunctional adaptor protein involved in important processes of cellular signaling, including innate immunity and apoptosis. TRAF family member-associated NF-kappaB activator (TANK) has been identified as a competitive intracellular inhibitor of TRAF2 function. Although TRAF recognition by various receptors has been studied extensively in the field of TRAF-mediated biology, molecular and functional details of TANK recognition and interaction with TRAF1 have not been studied. In this study, we report the crystal structure of the TRAF1/TANK peptide complex. Quantitative interaction experiments showed that TANK peptide interacts with both TRAF1 and TRAF2 with similar affinity in a micromolar range. Our structural study also reveals that TANK binds TRAF1 using a minor minimal consensus motif for TRAF binding, Px(Q/E)xT.



Coordinate and structural factor were deposited in the Protein Data Bank under PDB ID code 5H10.
Department of Chemistry and Biochemistry, Graduate School of Biochemistry, Yeungnam University, Gyeongsan, South Korea.
Chang Min
CM
Kim
Pohang Accelerator Laboratory, Pohang University of Science and Technology, South Korea.
Jae-Hee
JH
Jeong
New Drug Development Center, Daegu-Gyungpook Medical Innovation Foundation, South Korea.
Young-Jin
YJ
Son
Department of Metrology for Quality of Life, Center for Bioanalysis, Korea Research Institute of Standards and Science, Daejeon, South Korea.
Jun-Hyuk
JH
Choi
New Drug Development Center, Daegu-Gyungpook Medical Innovation Foundation, South Korea.
Sunghwan
S
Kim
Department of Chemistry and Biochemistry, Graduate School of Biochemistry, Yeungnam University, Gyeongsan, South Korea.
Hyun Ho
HH
Park
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D047990:TNF Receptor-Associated Factor 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C101338:PSMD2 protein, human; D011994:Recombinant Proteins; C484406:TANK protein, human; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2

TANK
; TRAF domain; TRAF1; apoptosis; crystal structure; inflammation