Gamma-adaptin appendage domain: structure and binding site for Eps15 and gamma-synergin.
The AP1 complex is one of a family of heterotetrameric clathrin-adaptor complexes involved in vesicular trafficking between the Golgi and endosomes. The complex has two large subunits, gamma and beta1, which can be divided into trunk, hinge, and appendage domains. The 1.8 A resolution structure of the gamma appendage is presented. The binding site for the known gamma appendage ligand gamma-synergin is mapped through creation of point mutations designed on the basis of the structure. We also show that Eps15, a protein believed to be involved in vesicle formation at the plasma membrane, is also a ligand of gamma appendage and binds to the same site as gamma-synergin. This observation explains the demonstrated brefeldinA (BFA)-sensitive colocalization of Eps15 and AP1 at the Golgi complex.
Kent
Helen M
HM
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
McMahon
Harvey T
HT
Evans
Philip R
PR
Benmerah
Alexandre
A
Owen
David J
DJ
D033961:Adaptor Protein Complex 1; D033982:Adaptor Protein Complex gamma Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020126:Brefeldin A / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006056:Golgi Apparatus / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010750:Phosphoproteins / Q000378:metabolism*; D017354:Point Mutation; D011487:Protein Conformation; D017510:Protein Folding; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment
D033961:Adaptor Protein Complex 1; D033982:Adaptor Protein Complex gamma Subunits; D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C486206:EPS15 protein, human; C082729:Eps15 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D010750:Phosphoproteins; D011500:Protein Synthesis Inhibitors; D011993:Recombinant Fusion Proteins; C121510:SYNRG protein, human; C498482:Synrg protein, rat; D020126:Brefeldin A