title: Crystal structure of syndesmos and its interaction with Syndecan-4 proteoglycan.
abstract: Syndesmos, nucleoside diphosphate linked moiety X (nudix)-type motif 16-like 1 (Nudt16l1), is evolutionarily divergent from the Nudt16 family. Syndesmos, which is co-localized with syndecan-4 cytoplasmic domain (Syn4(cyto)) in focal contacts, interacts with various cell adhesion adaptor proteins to control cell signaling. We determined the X-ray crystal structure of syndesmos; it is composed of seven α-helices and seven β-strands. Although syndesmos has a molecular topology similar to that of nudix hydrolase proteins, the structure of the nudix motif differs from that of X29. The dimeric interface of syndesmos is composed of α-helix 4, 7 and β-strand 2, 7, which primarily form hydrophobic interactions. The binding interaction between syndesmos and syn4(cyto) was characterized as a low-affinity interaction (Kd = 62 μM) by surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR). The NMR resonances of Lys (177, 178, 179), Gly182, and Ser183 in the C1 region and Lys193 and Lys194 in the V region of syndecan-4 are perturbed upon syndesmos binding. Our results provide structural insight into the molecular function of syndesmos in the regulation of cell signaling via binding to syndecan-4.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, South Korea.
authors.forename: Heeyoun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, South Korea.
authors.forename: Jiho
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, South Korea.
authors.forename: Inhwan
authors.initials: I
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, South Korea.
authors.forename: Ying Jin
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, South Korea. Electronic address: hscho8@yonsei.ac.kr.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, South Korea. Electronic address: wlee@spin.yonsei.ac.kr.
authors.forename: Weontae
authors.initials: W
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D011755:Pyrophosphatases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D053671:Syndecan-4 / Q000737:chemistry / Q000378:metabolism*
chemical_list: C508306:Sdc4 protein, mouse; D053671:Syndecan-4; C549897:NUDT16 protein, mouse; D011755:Pyrophosphatases
keywords: NMR spectroscopy; Nudix hydrolase; Syndecan-4; Syndesmos; X-ray crystallography