Crystal structure of the intraflagellar transport complex 25/27

EMBO J. 2011 May 18;30(10):1907-18. doi: 10.1038/emboj.2011.110. Epub 2011 Apr 19.

Abstract

The cilium is an important organelle that is found on many eukaryotic cells, where it serves essential functions in motility, sensory reception and signalling. Intraflagellar transport (IFT) is a vital process for the formation and maintenance of cilia. We have determined the crystal structure of Chlamydomonas reinhardtii IFT25/27, an IFT sub-complex, at 2.6 Å resolution. IFT25 and IFT27 interact via a conserved interface that we verify biochemically using structure-guided mutagenesis. IFT27 displays the fold of Rab-like small guanosine triphosphate hydrolases (GTPases), binds GTP and GDP with micromolar affinity and has very low intrinsic GTPase activity, suggesting that it likely requires a GTPase-activating protein (GAP) for robust GTP turnover. A patch of conserved surface residues contributed by both IFT25 and IFT27 is found adjacent to the GTP-binding site and could mediate the binding to other IFT proteins as well as to a potential GAP. These results provide the first step towards a high-resolution structural understanding of the IFT complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Chlamydomonas reinhardtii / chemistry*
  • Chlamydomonas reinhardtii / genetics
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Protein Structure, Quaternary
  • Sequence Homology, Amino Acid

Substances

  • Carrier Proteins
  • Guanosine Diphosphate
  • Guanosine Triphosphate

Associated data

  • PDB/2YC2
  • PDB/2YC4