TY - JOUR
T1 - Dual engagement regulation of protein interactions with the AP-2 adaptor α appendage
AU - Mishra, Sanjay K.
AU - Hawryluk, Matthew J.
AU - Brett, Tom J.
AU - Keyel, Peter A.
AU - Dupin, Amie L.
AU - Jha, Anupma
AU - Heuser, John E.
AU - Fremont, Daved H.
AU - Traub, Linton M.
PY - 2004/10/29
Y1 - 2004/10/29
N2 - Clathrin-mediated endocytosis depends upon the coordinated assembly of a large number of discrete clathrin coat components to couple cargo selection with rapid internalization from the cell surface. Accordingly, the heterotetrameric AP-2 adaptor complex binds not only to clathrin and select cargo molecules, but also to an extensive family of endocytic accessory factors and alternate sorting adaptors. Physical associations between accessory proteins and AP-2 occur primarily through DP(F/W) or FXDXF motifs, which engage an interaction surface positioned on the C-terminal platform subdomain of the independently folded α subunit appendage. Here, we find that the WXX(F/W)X(D/E) interaction motif found in several endocytic proteins, including synaptojanin 1, stonin 2, AAK1, GAK, and NE-CAP1, binds a second interaction site on the bilobal α appendage, located on the N-terminal β sandwich subdomain. Both α appendage binding sites can be engaged synchronously, and our data reveal that varied assemblies of interaction motifs with different affinities for two sites upon the α appendage can provide a mechanism for temporal ordering of endocytic accessory proteins during clathrin-mediated endocytosis.
AB - Clathrin-mediated endocytosis depends upon the coordinated assembly of a large number of discrete clathrin coat components to couple cargo selection with rapid internalization from the cell surface. Accordingly, the heterotetrameric AP-2 adaptor complex binds not only to clathrin and select cargo molecules, but also to an extensive family of endocytic accessory factors and alternate sorting adaptors. Physical associations between accessory proteins and AP-2 occur primarily through DP(F/W) or FXDXF motifs, which engage an interaction surface positioned on the C-terminal platform subdomain of the independently folded α subunit appendage. Here, we find that the WXX(F/W)X(D/E) interaction motif found in several endocytic proteins, including synaptojanin 1, stonin 2, AAK1, GAK, and NE-CAP1, binds a second interaction site on the bilobal α appendage, located on the N-terminal β sandwich subdomain. Both α appendage binding sites can be engaged synchronously, and our data reveal that varied assemblies of interaction motifs with different affinities for two sites upon the α appendage can provide a mechanism for temporal ordering of endocytic accessory proteins during clathrin-mediated endocytosis.
UR - http://www.scopus.com/inward/record.url?scp=8544266082&partnerID=8YFLogxK
U2 - 10.1074/jbc.M408095200
DO - 10.1074/jbc.M408095200
M3 - Article
C2 - 15292237
AN - SCOPUS:8544266082
SN - 0021-9258
VL - 279
SP - 46191
EP - 46203
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -