A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.
Clathrin-mediated endocytosis plays a major role in retrieving synaptic vesicles from the plasma membrane following exocytosis. This endocytic process requires AP180 (or a homolog), which promotes the assembly and restricts the size of clathrin-coated vesicles. The highly conserved 33 kDa amino-terminal domain of AP180 plays a critical role in binding to phosphoinositides and in regulating the clathrin assembly activity of AP180. The crystal structure of the amino-terminal domain reported herein reveals a novel fold consisting of a large double layer of sheets of ten alpha helices and a unique site for binding phosphoinositides. The finding that the clathrin-box motif is mostly buried and lies in a helix indicates a different site and mechanism for binding of the domain to clathrins than previously assumed.
Mao
Y
Y
Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA.
Chen
J
J
Maynard
J A
JA
Zhang
B
B
Quiocho
F A
FA
D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004705:Endocytosis; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D020033:Protein Isoforms; C439023:clathrin assembly protein AP180