Crystal structure of γ-tubulin complex protein GCP4 provides insight into microtubule nucleation

Nat Struct Mol Biol. 2011 Jul 3;18(8):915-9. doi: 10.1038/nsmb.2083.

Abstract

Microtubule nucleation in all eukaryotes involves γ-tubulin small complexes (γTuSCs) that comprise two molecules of γ-tubulin bound to γ-tubulin complex proteins (GCPs) GCP2 and GCP3. In many eukaryotes, multiple γTuSCs associate with GCP4, GCP5 and GCP6 into large γ-tubulin ring complexes (γTuRCs). Recent cryo-EM studies indicate that a scaffold similar to γTuRCs is formed by lateral association of γTuSCs, with the C-terminal regions of GCP2 and GCP3 binding γ-tubulin molecules. However, the exact role of GCPs in microtubule nucleation remains unknown. Here we report the crystal structure of human GCP4 and show that its C-terminal domain binds directly to γ-tubulin. The human GCP4 structure is the prototype for all GCPs, as it can be precisely positioned within the γTuSC envelope, revealing the nature of protein-protein interactions and conformational changes regulating nucleation activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / physiology
  • Microtubules / metabolism*
  • Protein Interaction Domains and Motifs
  • Protein Structure, Tertiary
  • Tubulin / metabolism

Substances

  • Microtubule-Associated Proteins
  • TUBGCP4 protein, human
  • Tubulin

Associated data

  • PDB/3RIP