7RD5
Crystal structure of Tspan15 large extracellular loop (Tspan15 LEL) in complex with 1C12 Fab
Summary for 7RD5
| Entry DOI | 10.2210/pdb7rd5/pdb |
| Related | 7RDB |
| Descriptor | 1C12 Fab Light Chain, 1C12 Fab Heavy Chain, Tetraspanin-15 (3 entities in total) |
| Functional Keywords | tetraspanin, membrane protein, protein trafficking, cell adhesion |
| Biological source | Mus musculus (mouse) More |
| Total number of polymer chains | 6 |
| Total formula weight | 126423.63 |
| Authors | Lipper, C.H.,Gabriel, K.H.,Seegar, T.C.M.,Durr, K.L.,Tomlinson, M.G.,Blacklow, S.C. (deposition date: 2021-07-09, release date: 2021-11-03, Last modification date: 2024-11-13) |
| Primary citation | Lipper, C.H.,Gabriel, K.H.,Seegar, T.C.M.,Durr, K.L.,Tomlinson, M.G.,Blacklow, S.C. Crystal structure of the Tspan15 LEL domain reveals a conserved ADAM10 binding site. Structure, 30:206-214.e4, 2022 Cited by PubMed Abstract: Tetraspanins are four-pass transmembrane proteins that function by regulating trafficking of partner proteins and organizing signaling complexes in the membrane. Tspan15, one of a six-member TspanC8 subfamily, forms a complex that regulates the trafficking, maturation, and substrate selectivity of the transmembrane protease ADAM10, an essential enzyme in mammalian physiology that cleaves a wide variety of membrane-anchored substrates, including Notch receptors, amyloid precursor protein, cadherins, and growth factors. We present here crystal structures of the Tspan15 large extracellular loop (LEL) required for functional association with ADAM10 both in isolation and in complex with the Fab fragment of an anti-Tspan15 antibody. Comparison of the Tspan15 LEL with other tetraspanin LEL structures shows that a core helical framework buttresses a variable region that structurally diverges among LELs. Using co-immunoprecipitation and a cellular N-cadherin cleavage assay, we identify a site on Tspan15 required for both ADAM10 binding and promoting substrate cleavage. PubMed: 34739841DOI: 10.1016/j.str.2021.10.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.6 Å) |
Structure validation
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