Download MendeleyThe CAP-Gly domain of CYLD associates with the proline-rich sequence in NEMO/IKKgamma
Saito, K., Kigawa, T., Koshiba, S., Sato, K., Matsuo, Y., Sakamoto, A., Takagi, T., Shirouzu, M., Yabuki, T., Nunokawa, E., Seki, E., Matsuda, T., Aoki, M., Miyata, Y., Hirakawa, N., Inoue, M., Terada, T., Nagase, T., Kikuno, R., Nakayama, M., Ohara, O., Tanaka, A., Yokoyama, S.(2004) Structure 12: 1719-1728
- PubMed: 15341735
- DOI: https://doi.org/10.1016/j.str.2004.07.012
- Primary Citation of Related Structures:
1IXD - PubMed Abstract:
CYLD was originally identified as the human familial cylindromatosis tumor suppressor. Recently, it was reported that CYLD directly interacts with NEMO/IKKgamma and TRAF2 in the NF-kappaB signaling pathway. The two proteins bind to a region of CYLD that contains a Cys-box motif and the third cytoskeleton-associated protein-glycine conserved (CAP-Gly) domain. Here we report that the third CAP-Gly domain of CYLD specifically interacts with one of the two proline-rich sequences of NEMO/IKKgamma. The tertiary structure of the CAP-Gly domain shares the five-stranded beta sheet topology with the SH3 domain, which is well known as a proline-rich sequence-recognition domain. However, chemical shift mapping revealed that the peptide binding site of the CAP-Gly domain is formed without the long peptide binding loop characteristic of the SH3 domain. Therefore, CAP-Gly is likely to be a novel proline-rich sequence binding domain with a mechanism different from that of the SH3 domain.
Organizational Affiliation:
RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
