Structural basis for Rab11-dependent membrane recruitment of a family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1

Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15416-21. doi: 10.1073/pnas.0605357103. Epub 2006 Oct 9.

Abstract

Family of Rab11-interacting protein (FIP)3/Arfophlin-1 and FIP4/Arfophilin-2 are dual effectors for Rab11 and ADP ribosylation factor (ARF)5/ARF6, which are involved in membrane delivery from recycling endosomes to the plasma membrane during cytokinesis. Here, we define the distinct C-terminal binding regions of FIP3 and FIP4 for Rab11 and ARF5/ARF6. Furthermore, we determined the crystal structure of Rab11 in complex with the Rab11-binding domain (RBD) of FIP3. The long amphiphilic alpha-helix of FIP3-RBD forms a parallel coiled-coil homodimer, with two symmetric interfaces with two Rab11 molecules. The hydrophobic side of the RBD helix is involved in homodimerization and mediates the interaction with the Rab11 switch 1 region, whereas the opposite hydrophilic side interacts with the Rab11 switch 2 and is the major factor contributing to the binding specificity. The bivalent interaction of FIP3 with Rab11 at the C terminus allows FIP3 to coordinately function with other binding partners, including ARFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary*
  • Sequence Alignment
  • rab GTP-Binding Proteins / chemistry*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Carrier Proteins
  • Protein Isoforms
  • arfophilin
  • rab11 protein
  • ADP-Ribosylation Factors
  • rab GTP-Binding Proteins

Associated data

  • PDB/2D7C