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Novel Binding Sites on Clathrin and Adaptors Regulate Distinct Aspects of Coat Assembly
Author(s) -
Knuehl Christine,
Chen ChihYing,
Manalo Venus,
Hwang Peter K.,
Ota Nobuyuki,
Brodsky Frances M.
Publication year - 2006
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2006.00499.x
Subject(s) - biology , clathrin , coat , coat protein , microbiology and biotechnology , computational biology , genetics , endocytosis , ecology , receptor , rna , gene
Clathrin‐coated vesicles (CCVs) sort proteins at the plasma membrane, endosomes and trans Golgi network for multiple membrane traffic pathways. Clathrin recruitment to membranes and its self‐assembly into a polyhedral coat depends on adaptor molecules, which interact with membrane‐associated vesicle cargo. To determine how adaptors induce clathrin recruitment and assembly, we mapped novel interaction sites between these coat components. A site in the ankle domain of the clathrin triskelion leg was identified that binds a common site on the appendages of tetrameric [AP1 and AP2] and monomeric (GGA1) adaptors. Mutagenesis and modeling studies suggested that the clathrin–GGA1 appendage interface is nonlinear, unlike other peptide–appendage interactions, but overlaps with a sandwich domain binding site for accessory protein peptides, allowing for competitive regulation of coated vesicle formation. A novel clathrin box in the GGA1 hinge region was also identified and shown to mediate membrane recruitment of clathrin, while disruption of the clathrin–GGA1 appendage interaction did not affect recruitment. Thus, the distinct sites for clathrin–adaptor interactions perform distinct functions, revealing new aspects to regulation of CCV formation.