Two distinct interaction motifs in amphiphysin bind two independent sites on the clathrin terminal domain beta-propeller

Nat Struct Mol Biol. 2004 Mar;11(3):242-8. doi: 10.1038/nsmb736. Epub 2004 Feb 15.


During the assembly of clathrin-coated vesicles, many peripheral membrane proteins, including the amphiphysins, use LLDLD-type clathrin-box motifs to interact with the N-terminal beta-propeller domain (TD) of clathrin. The 2.3 A-resolution structure of the clathrin TD in complex with a TLPWDLWTT peptide from amphiphysin 1 delineates a second clathrin-binding motif, PWXXW (the W box), that binds at a site on the TD remote from the clathrin box-binding site. The presence of both sequence motifs within the unstructured region of the amphiphysins allows them to bind more tightly to free TDs than do other endocytic proteins that contain only clathrin-box motifs. This property, along with the propensity of the N-terminal BAR domain to bind curved membranes, will preferentially localize amphiphysin and its partner, dynamin, to the periphery of invaginated clathrin lattices.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • Cattle
  • Clathrin / chemistry*
  • Clathrin / genetics
  • Clathrin / metabolism
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / metabolism
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / metabolism
  • Peptide Fragments / chemistry
  • Protein Binding
  • Protein Structure, Tertiary


  • Clathrin
  • Molecular Motor Proteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • amphiphysin