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Structural basis for the accessory protein recruitment by the γ-adaptin ear domain

Abstract

The adaptor proteins AP-1 and GGA regulate membrane traffic between the trans-Golgi network (TGN) and endosomes/lysosomes through ARF-regulated membrane association, recognition of sorting signals, and recruitment of clathrin and accessory proteins. The γ1-adaptin subunits of AP-1 and GGA possess homologous ear domains involved in the recruitment of accessory proteins, γ-synergin and Rabaptin-5. The crystal structure of the human γ1-adaptin ear domain consists solely of an immunoglobulin-like fold, unlike the α-adaptin ear domain. Structure-based mutational analyses reveal a binding site for the accessory proteins that is composed of conserved basic residues, indicating that the recruitment mechanism in γ1-adaptin and GGA is distinct from that in α-adaptin.

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Figure 1: Structure of the human γ1-ear domain.
Figure 2: Structure of the α-adaptin ear and β2-adaptin ear domains.
Figure 3: Conserved basic surface.
Figure 4: Pull-down assay.

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GenBank/EMBL/DDBJ

Protein Data Bank

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, from the Japan Society for Promotion of Science (fellowship to H.T.) and from the University of Tsukuba Research Projects.

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Correspondence to Soichi Wakatsuki.

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The authors declare no competing financial interests.

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Nogi, T., Shiba, Y., Kawasaki, M. et al. Structural basis for the accessory protein recruitment by the γ-adaptin ear domain. Nat Struct Mol Biol 9, 527–531 (2002). https://doi.org/10.1038/nsb808

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