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Crystal structure of human tetraspanin CD81
Structural highlights
DiseaseCD81_HUMAN Defects in CD81 are the cause of immunodeficiency common variable type 6 (CVID6) [MIM:613496; also called antibody deficiency due to CD81 defect. CVID6 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.[1] FunctionCD81_HUMAN May play an important role in the regulation of lymphoma cell growth. Interacts with a 16-kDa Leu-13 protein to form a complex possibly involved in signal transduction. May act as the viral receptor for HCV. Publication Abstract from PubMedTetraspanins 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. Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket.,Zimmerman B, Kelly B, McMillan BJ, Seegar TC, Dror RO, Kruse AC, Blacklow SC Cell. 2016 Nov 3;167(4):1041-1051.e11. doi: 10.1016/j.cell.2016.09.056. Epub 2016, Oct 27. PMID:27881302[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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