Crystal Structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 Complexes: Affinity, Specificity, and Regulation

Journal Article · Fri Jan 01 04:00:00 EST 2010 · Molecular Cell

DOI:https://doi.org/10.1016/j.molcel.2010.03.009· OSTI ID:1019854

Zheng, C; Kabaleeswaran, V; Wang, Y; Cheng, G; Wu, H

TRAF1/2 and cIAP1/2 are members of the TNF receptor-associated factor (TRAF) and the inhibitor of apoptosis (IAP) families, respectively. They are critical for canonical and noncanonical NF-{kappa}B signaling pathways. Here, we report the crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes. A TRAF2 trimer interacts with one cIAP2 both in the crystal and in solution. Two chains of the TRAF2 trimer directly contact cIAP2, and key residues at the interface are confirmed by mutagenesis. TRAF1 and TRAF2 preferentially form the TRAF1: (TRAF2)2 heterotrimer, which interacts with cIAP2 more strongly than TRAF2 alone. In contrast, TRAF1 alone interacts very weakly with cIAP2. Surprisingly, TRAF1 and one chain of TRAF2 in the TRAF1: (TRAF2)2: cIAP2 ternary complex mediate interaction with cIAP2. Because TRAF1 is upregulated by many stimuli, it may modulate the interaction of TRAF2 with cIAP1/2, which explains regulatory roles of TRAF1 in TNF signaling.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1019854
• Report Number(s): BNL--95813-2011-JA
• Journal Information: Molecular Cell, Journal Name: Molecular Cell Journal Issue: 1 Vol. 38; ISSN 1097-2765
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AFFINITY
APOPTOSIS
CHAINS
CRYSTAL STRUCTURE
MUTAGENESIS
REGULATIONS
RESIDUES
SPECIFICITY
STIMULI
national synchrotron light source