5TCX

Crystal structure of human tetraspanin CD81

Summary for 5TCX

• Entry DOI: 10.2210/pdb5tcx/pdb
• Descriptor: CD81 antigen, CHOLESTEROL (3 entities in total)
• Functional Keywords: tetraspanin, transmembrane, cholesterol, cell invasion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 27590.24

Authors

Zimmerman, B.,McMillan, B.J.,Seegar, T.C.M.,Kruse, A.C.,Blacklow, S.C. (deposition date: 2016-09-16, release date: 2016-11-09, Last modification date: 2023-10-04)

Primary citation

Zimmerman, B.,Kelly, B.,McMillan, B.J.,Seegar, T.C.,Dror, R.O.,Kruse, A.C.,Blacklow, S.C.
Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket.
Cell, 167:1041-1051.e11, 2016

PubMed Abstract: Tetraspanins comprise a diverse family of four-pass transmembrane proteins that play critical roles in the immune, reproductive, genitourinary, and auditory systems. Despite their pervasive roles in human physiology, little is known about the structure of tetraspanins or the molecular mechanisms underlying their various functions. Here, we report the crystal structure of human CD81, a full-length tetraspanin. The transmembrane segments of CD81 pack as two largely separated pairs of helices, capped by the large extracellular loop (EC2) at the outer membrane leaflet. The two pairs of helices converge at the inner leaflet to create an intramembrane pocket with additional electron density corresponding to a bound cholesterol molecule within the cavity. Molecular dynamics simulations identify an additional conformation in which EC2 separates substantially from the transmembrane domain. Cholesterol binding appears to modulate CD81 activity in cells, suggesting a potential mechanism for regulation of tetraspanin function.

PubMed: 27881302
DOI: 10.1016/j.cell.2016.09.056

Experimental method

X-RAY DIFFRACTION (2.955 Å)