title: The CAP-Gly domain of CYLD associates with the proline-rich sequence in NEMO/IKKgamma.
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.
authors.affiliation: RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Saito
authors.forename: Takanori
authors.initials: T
authors.lastname: Kigawa
authors.forename: Seizo
authors.initials: S
authors.lastname: Koshiba
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sato
authors.forename: Yo
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Ayako
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takagi
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Takashi
authors.initials: T
authors.lastname: Yabuki
authors.forename: Emi
authors.initials: E
authors.lastname: Nunokawa
authors.forename: Eiko
authors.initials: E
authors.lastname: Seki
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Aoki
authors.forename: Yukako
authors.initials: Y
authors.lastname: Miyata
authors.forename: Noriko
authors.initials: N
authors.lastname: Hirakawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Takaho
authors.initials: T
authors.lastname: Terada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagase
authors.forename: Reiko
authors.initials: R
authors.lastname: Kikuno
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakayama
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: 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
chemical_list: 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