7RDB

Crystal structure of Tspan15 large extracellular loop (Tspan15 LEL)

Summary for 7RDB

• Entry DOI: 10.2210/pdb7rdb/pdb
• Related: 7RD5
• Descriptor: Tetraspanin-15 (2 entities in total)
• Functional Keywords: tetraspanin, membrane protein, protein trafficking, cell adhesion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 24
• Total formula weight: 344285.64

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

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: 34739841
DOI: 10.1016/j.str.2021.10.007

Experimental method

X-RAY DIFFRACTION (2.52 Å)