Oligomerization of the Tetraspanin CD81 via the Flexibility of Its δ-Loop.
Tetraspanins are master organizers in the plasma membrane, forming tetraspanin-enriched microdomains with one another and other surface molecules. Their rod-shaped structure includes a large extracellular loop (LEL) that plays a pivotal role in tetraspanin network formation. We performed comparative atomistic and coarse-grain molecular-dynamics simulations of the LEL in isolation and full-length CD81, and reproduced LEL flexibility patterns known from wet-lab experiments in which the LEL δ-loop region showed a pronounced flexibility. In a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipid bilayer and a plasma membrane environment, the conformational flexibility of the δ-loop initiates CD81-CD81 contacts for oligomerization. Furthermore, in the plasma membrane, CD81-ganglioside bridges arising from preformed glycolipid patches cross-link the complexes. The data suggest that exposing a flexible domain enables binding to interaction partners by circumventing the restriction of orientation and conformational freedom of membrane proteins.
Membrane Biochemistry, Life and Medical Sciences Institute, Bonn, Germany. Electronic address: thomas.schmidt@uni-bonn.de.
Thomas H
TH
Schmidt
Membrane Biochemistry, Life and Medical Sciences Institute, Bonn, Germany.
Yahya
Y
Homsi
Membrane Biochemistry, Life and Medical Sciences Institute, Bonn, Germany. Electronic address: thorsten.lang@uni-bonn.de.
Thorsten
T
Lang
D002462:Cell Membrane / Q000378:metabolism; D004548:Elasticity / Q000502:physiology; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D060225:Tetraspanin 28 / Q000378:metabolism*
C554798:CD81 protein, human; D005732:Gangliosides; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D012997:Solvents; D060225:Tetraspanin 28; C028694:1-palmitoyl-2-oleoylphosphatidylcholine