Structural biology study of human TNF receptor associated factor 4 TRAF domain.
10.1007/s13238-013-3068-z
- Author:
Fengfeng NIU
1
;
Heng RU
1
;
Wei DING
1
;
Songying OUYANG
2
;
Zhi-Jie LIU
3
Author Information
1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ouyangsy@moon.ibp.ac.cn.
3. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. zjliu@ibp.ac.cn.
- Publication Type:Journal Article
- Keywords:
TRAF domain;
TRAF4;
additional loop;
crystal structure;
phosphorylation site
- MeSH:
Amino Acid Sequence;
Binding Sites;
Crystallography, X-Ray;
Humans;
Hydrophobic and Hydrophilic Interactions;
Models, Molecular;
Phosphorylation;
Protein Conformation, alpha-Helical;
Protein Domains;
Protein Structure, Quaternary;
Recombinant Proteins;
chemistry;
Sequence Homology, Amino Acid;
TNF Receptor-Associated Factor 4;
chemistry
- From:
Protein & Cell
2013;4(9):687-694
- CountryChina
- Language:English
-
Abstract:
TRAF4 is a unique member of TRAF family, which is essential for innate immune response, nervous system and other systems. In addition to be an adaptor protein, TRAF4 was identified as a regulator protein in recent studies. We have determined the crystal structure of TRAF domain of TRAF4 (residues 292-466) at 2.60 Å resolution by X-ray crystallography method. The trimericly assembled TRAF4 resembles a mushroom shape, containing a super helical "stalk" which is made of three right-handed intertwined α helixes and a C-terminal "cap", which is divided at residue L302 as a boundary. Similar to other TRAFs, both intermolecular hydrophobic interaction in super helical "stalk" and hydrogen bonds in "cap" regions contribute directly to the formation of TRAF4 trimer. However, differing from other TRAFs, there is an additional flexible loop (residues 421-426), which contains a previously identified phosphorylated site S426 exposing on the surface. This S426 was reported to be phosphorylated by IKKα which is the pre-requisite for TRAF4-NOD2 complex formation and thus to inhibit NOD2-induced NF-κB activation. Therefore, the crystal structure of TRAF4-TRAF is valuable for understanding its molecular basis for its special function and provides structural information for further studies.
