Structural Basis for the Lack of E2 Interaction in the RING Domain of TRAF2

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Biochemistry

DOI:https://doi.org/10.1021/bi901462e· OSTI ID:1019874

Yin, Q; Lamothe, B; Darnay, B; Wu, H

TRAF proteins are intracellular signal transducers for a number of immune receptor superfamilies. Specifically, TRAF2 interacts with members of the TNF receptor superfamily and connects the receptors to downstream signaling proteins. It has been assumed that TRAF2 is a ubiquitin ligase like TRAF6 and mediates K63-linked polyubiquitination of RIP1, a kinase pivotal in TNF{alpha}-induced NF-{kappa}B activation. Here we report the crystal structure of the RING and the first zinc finger domains of TRAF2. We show that the TRAF2 RING structure is very different from the known TRAF6 RING structure. The differences are multifaceted, including amino acid differences at the critical Ubc13-interacting site, local conformational differences, and a unique nine-residue insertion between the RING domain and the first zinc finger in TRAF2. These structural differences prevent TRAF2 from interacting with Ubc13 and other related E2s via steric clash and unfavorable interfaces. Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNF{alpha} signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-{kappa}B signaling.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1019874
• Report Number(s): BNL--95708-2011-JA
• Journal Information: Biochemistry, Journal Name: Biochemistry Journal Issue: 44 Vol. 48; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AMINO ACIDS
CRYSTAL STRUCTURE
LIGASES
PHOSPHOTRANSFERASES
PROTEINS
TRANSDUCERS
ZINC
national synchrotron light source