Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly

Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8907-12. doi: 10.1073/pnas.96.16.8907.

Abstract

AP-2 adaptors regulate clathrin-bud formation at the cell surface by recruiting clathrin trimers to the plasma membrane and by selecting certain membrane proteins for inclusion within the developing clathrin-coat structure. These functions are performed by discrete subunits of the adaptor heterotetramer. The carboxyl-terminal appendage of the AP-2 alpha subunit appears to regulate the translocation of several endocytic accessory proteins to the bud site. We have determined the crystal structure of the alpha appendage at 1.4-A resolution by multiwavelength anomalous diffraction phasing. It is composed of two distinct structural modules, a beta-sandwich domain and a mixed alpha-beta platform domain. Structure-based mutagenesis shows that alterations to the molecular surface of a highly conserved region on the platform domain differentially affect associations of the appendage with amphiphysin, eps15, epsin, and AP180, revealing a common protein-binding interface.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Sequence
  • Animals
  • Clathrin / chemistry
  • Clathrin / metabolism
  • Crystallography, X-Ray
  • Humans
  • Macromolecular Substances
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Monomeric Clathrin Assembly Proteins*
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / metabolism
  • Phosphoproteins / chemistry*
  • Phosphoproteins / metabolism
  • Protein Structure, Secondary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • Clathrin
  • Macromolecular Substances
  • Monomeric Clathrin Assembly Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • clathrin assembly protein AP180

Associated data

  • PDB/1QTP
  • PDB/1QTS