The CAP-Gly domain of CYLD associates with the proline-rich sequence in NEMO/IKKgamma.
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.
Saito
Kohei
K
RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
Kigawa
Takanori
T
Koshiba
Seizo
S
Sato
Kazuo
K
Matsuo
Yo
Y
Sakamoto
Ayako
A
Takagi
Tetsuo
T
Shirouzu
Mikako
M
Yabuki
Takashi
T
Nunokawa
Emi
E
Seki
Eiko
E
Matsuda
Takayoshi
T
Aoki
Masaaki
M
Miyata
Yukako
Y
Hirakawa
Noriko
N
Inoue
Makoto
M
Terada
Takaho
T
Nagase
Takahiro
T
Kikuno
Reiko
R
Nakayama
Manabu
M
Ohara
Osamu
O
Tanaka
Akiko
A
Yokoyama
Shigeyuki
S
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011392:Proline / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C491731:IKBKG protein, human; D010455:Peptides; D025521:Tumor Suppressor Proteins; D011392:Proline; D051550:I-kappa B Kinase; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD