Clathrin self-assembly is mediated by a tandemly repeated superhelix.
Clathrin is a triskelion-shaped cytoplasmic protein that polymerizes into a polyhedral lattice on intracellular membranes to form protein-coated membrane vesicles. Lattice formation induces the sorting of membrane proteins during endocytosis and organelle biogenesis by interacting with membrane-associated adaptor molecules. The clathrin triskelion is a trimer of heavy-chain subunits (1,675 residues), each binding a single light-chain subunit, in the hub domain (residues 1,074-1,675). Light chains negatively modulate polymerization so that intracellular clathrin assembly is adaptor-dependent. Here we report the atomic structure, to 2.6 A resolution, of hub residues 1,210-1,516 involved in mediating spontaneous clathrin heavy-chain polymerization and light-chain association. The hub fragment folds into an elongated coil of alpha-helices, and alignment analyses reveal a 145-residue motif that is repeated seven times along the filamentous leg and appears in other proteins involved in vacuolar protein sorting. The resulting model provides a three-dimensional framework for understanding clathrin heavy-chain self-assembly, light-chain binding and trimerization.
Ybe
J A
JA
The G. W. Hooper Foundation, Department of Microbiology and Immunology, University of California San Francisco, 94143, USA.
Brodsky
F M
FM
Hofmann
K
K
Lin
K
K
Liu
S H
SH
Chen
L
L
Earnest
T N
TN
Fletterick
R J
RJ
Hwang
P K
PK
D000595:Amino Acid Sequence; D000818:Animals; D002966:Clathrin / Q000737:chemistry*; D003461:Crystallography; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020449:Repetitive Sequences, Amino Acid
D002966:Clathrin