Crystal structure of syndesmos and its interaction with Syndecan-4 proteoglycan.
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.
['Kim|Heeyoun|H|', 'Yoo|Jiho|J|', 'Lee|Inhwan|I|', 'Kang|Ying Jin|YJ|', 'Cho|Hyun-Soo|HS|', 'Lee|Weontae|W|']
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 D017386:Sequence Homology, Amino Acid D020349:Surface Plasmon Resonance D053671:Syndecan-4
Syndesmos Syndecan-4 Nudix hydrolase NMR spectroscopy X-ray crystallography