Structural and functional analysis of the globular head domain of p115 provides insight into membrane tethering

J Mol Biol. 2009 Aug 7;391(1):26-41. doi: 10.1016/j.jmb.2009.04.062. Epub 2009 May 4.


Molecular tethers have a central role in the organization of the complex membrane architecture of eukaryotic cells. p115 is a ubiquitous, essential tether involved in vesicle transport and the structural organization of the exocytic pathway. We describe two crystal structures of the N-terminal domain of p115 at 2.0 A resolution. The p115 structures show a novel alpha-solenoid architecture constructed of 12 armadillo-like, tether-repeat, alpha-helical tripod motifs. We find that the H1 TR binds the Rab1 GTPase involved in endoplasmic reticulum to Golgi transport. Mutation of the H1 motif results in the dominant negative inhibition of endoplasmic reticulum to Golgi trafficking. We propose that the H1 helical tripod contributes to the assembly of Rab-dependent complexes responsible for the tether and SNARE-dependent fusion of membranes.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Crystallography, X-Ray
  • Golgi Matrix Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation, Missense
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Vesicular Transport Proteins / chemistry*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • rab1 GTP-Binding Proteins / metabolism


  • Golgi Matrix Proteins
  • Vesicular Transport Proteins
  • vesicular transport factor p115
  • rab1 GTP-Binding Proteins

Associated data

  • PDB/3GQ2
  • PDB/3GRL