Structural basis for tetraspanin functions as revealed by the cryo-EM structure of uroplakin complexes at 6-A resolution.
Tetraspanin uroplakins (UPs) Ia and Ib, together with their single-spanning transmembrane protein partners UP II and IIIa, form a unique crystalline 2D array of 16-nm particles covering almost the entire urothelial surface. A 6 A-resolution cryo-EM structure of the UP particle revealed that the UP tetraspanins have a rod-shaped structure consisting of four closely packed transmembrane helices that extend into the extracellular loops, capped by a disulfide-stabilized head domain. The UP tetraspanins form the primary complexes with their partners through tight interactions of the transmembrane domains as well as the extracellular domains, so that the head domains of their tall partners can bridge each other at the top of the heterotetramer. The secondary interactions between the primary complexes and the tertiary interaction between the 16-nm particles contribute to the formation of the UP tetraspanin network. The rod-shaped tetraspanin structure allows it to serve as stable pilings in the lipid sea, ideal for docking partner proteins to form structural/signaling networks.
Min
Guangwei
G
Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
Wang
Huaibin
H
Sun
Tung-Tien
TT
Kong
Xiang-Peng
XP
D000818:Animals; D003198:Computer Simulation; D020285:Cryoelectron Microscopy; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure*; D051379:Mice; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D059470:Tetraspanins; D060170:Uroplakin II; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D059470:Tetraspanins; C490123:Upk1a protein, mouse; C490124:Upk1b protein, mouse; C554659:Upk2 protein, mouse; D060170:Uroplakin II; D060171:Uroplakin III; D060167:Uroplakin Ia; D060169:Uroplakin Ib