Abstract
The GGAs are a family of clathrin adaptor proteins involved in vesicular transport between the trans-Golgi network and endosomal system. Here we confirm reports that GGAs are targeted to the Golgi via interaction between the GGA-GAT domain and ARF-GTP, and we present the structure of the GAT domain of human GGA1, completing the structural description of the folded domains of GGA proteins. The GGA-GAT domain possesses an all alpha-helical fold with a "paper clip" topology comprising two independent subdomains. Structure-based mutagenesis demonstrates that ARF1-GTP binding by GGAs is exclusively governed by the N-terminal "hook" subdomain, and, using an in vitro recruitment assay, we show that ARF-GTP binding by this small structure is required and sufficient for Golgi targeting of GGAs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP-Ribosylation Factor 1 / metabolism*
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ADP-Ribosylation Factors / metabolism*
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Adaptor Proteins, Vesicular Transport*
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Amino Acid Sequence / physiology
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Animals
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Carrier Proteins / metabolism*
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Cell Compartmentation / physiology
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Cells, Cultured
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Clathrin-Coated Vesicles / metabolism*
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Clathrin-Coated Vesicles / ultrastructure
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Eukaryotic Cells / cytology
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Eukaryotic Cells / metabolism*
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Humans
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Intracellular Membranes / metabolism
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Molecular Sequence Data
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Protein Binding / physiology
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Protein Structure, Tertiary / physiology
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Protein Transport / physiology*
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Rats
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Swine
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trans-Golgi Network / metabolism*
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trans-Golgi Network / ultrastructure
Substances
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Adaptor Proteins, Vesicular Transport
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Carrier Proteins
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GGA adaptor proteins
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ADP-Ribosylation Factor 1
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ADP-Ribosylation Factors