Structural basis of Rab5-Rabaptin5 interaction in endocytosis

Nat Struct Mol Biol. 2004 Oct;11(10):975-83. doi: 10.1038/nsmb832. Epub 2004 Sep 19.


Rab5 is a small GTPase that regulates early endosome fusion. We present here the crystal structure of the Rab5 GTPase domain in complex with a GTP analog and the C-terminal domain of effector Rabaptin5. The proteins form a dyad-symmetric Rab5-Rabaptin5(2)-Rab5 ternary complex with a parallel coiled-coil Rabaptin5 homodimer in the middle. Two Rab5 molecules bind independently to the Rabaptin5 dimer using their switch and interswitch regions. The binding does not involve the Rab complementarity-determining regions. We also present the crystal structures of two distinct forms of GDP-Rab5 complexes, both of which are incompatible with Rabaptin5 binding. One has a dislocated and disordered switch I but a virtually intact switch II, whereas the other has its beta-sheet and both switch regions reorganized. Biochemical and functional analyses show that the crystallographically observed Rab5-Rabaptin5 complex also exists in solution, and disruption of this complex by mutation abrogates endosome fusion.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Endocytosis*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / metabolism*
  • rab GTP-Binding Proteins / chemistry
  • rab GTP-Binding Proteins / metabolism*
  • rab5 GTP-Binding Proteins / chemistry
  • rab5 GTP-Binding Proteins / metabolism*


  • Vesicular Transport Proteins
  • rab GTP-Binding Proteins
  • rab5 GTP-Binding Proteins

Associated data

  • PDB/1TU3
  • PDB/1TU4