Structural basis for Rab11-mediated recruitment of FIP3 to recycling endosomes

J Mol Biol. 2006 Nov 24;364(2):121-35. doi: 10.1016/j.jmb.2006.08.064. Epub 2006 Aug 26.


The Rab11 GTPase regulates recycling of internalized plasma membrane receptors and is essential for completion of cytokinesis. A family of Rab11 interacting proteins (FIPs) that conserve a C-terminal Rab-binding domain (RBD) selectively recognize the active form of Rab11. Normal completion of cytokinesis requires a complex between Rab11 and FIP3. Here, we report the crystal structure and mutational analysis of a heterotetrameric complex between constitutively active Rab11 and a FIP3 construct that includes the RBD. Two Rab11 molecules bind to dyad symmetric sites at the C terminus of FIP3, which forms a non-canonical coiled-coiled dimer with a flared C terminus and hook region. The RBD overlaps with the coiled coil and extends through the C-terminal hook. Although FIP3 engages the switch and interswitch regions of Rab11, the mode of interaction differs significantly from that of other Rab-effector complexes. In particular, the switch II region undergoes a large structural rearrangement from an ordered but non-complementary active conformation to a remodeled conformation that facilitates the interaction with FIP3. Finally, we provide evidence that FIP3 can form homo-oligomers in cells, and that a critical determinant of Rab11 binding in vitro is necessary for FIP3 recruitment to recycling endosomes during cytokinesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Cell Membrane / metabolism
  • Endosomes / metabolism*
  • Green Fluorescent Proteins / genetics
  • HeLa Cells
  • Humans
  • I-kappa B Kinase / chemistry*
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein Conformation
  • Protein Transport
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • rab GTP-Binding Proteins / chemistry*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / physiology


  • IKBKG protein, human
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • I-kappa B Kinase
  • rab11 protein
  • rab GTP-Binding Proteins

Associated data

  • PDB/2HV8