Structure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes

Biochemistry. 2000 Sep 19;39(37):11282-90. doi: 10.1021/bi0013546.


VHS domains are found at the N-termini of select proteins involved in intracellular membrane trafficking. We have determined the crystal structure of the VHS domain of the human Tom1 (target of myb 1) protein to 1.5 A resolution. The domain consists of eight helices arranged in a superhelix. The surface of the domain has two main features: (1) a basic patch on one side due to several conserved positively charged residues on helix 3 and (2) a negatively charged ridge on the opposite side, formed by residues on helix 2. We compare our structure to the recently obtained structure of tandem VHS-FYVE domains from Hrs [Mao, Y., Nickitenko, A., Duan, X., Lloyd, T. E., Wu, M. N., Bellen, H., and Quiocho, F. A. (2000) Cell 100, 447-456]. Key features of the interaction surface between the FYVE and VHS domains of Hrs, involving helices 2 and 4 of the VHS domain, are conserved in the VHS domain of Tom1, even though Tom1 does not have a FYVE domain. We also compare the structures of the VHS domains of Tom1 and Hrs to the recently obtained structure of the ENTH domain of epsin-1 [Hyman, J., Chen, H., Di Fiore, P. P., De Camilli, P., and Brünger, A. T. (2000) J. Cell Biol. 149, 537-546]. Comparison of the two VHS domains and the ENTH domain reveals a conserved surface, composed of helices 2 and 4, that is utilized for protein-protein interactions. In addition, VHS domain-containing proteins are often localized to membranes. We suggest that the conserved positively charged surface of helix 3 in VHS and ENTH domains plays a role in membrane binding.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Sequence
  • Carrier Proteins / chemistry*
  • Conserved Sequence
  • Crystallography, X-Ray
  • Endosomal Sorting Complexes Required for Transport
  • Genes, myb
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Neuropeptides / chemistry
  • Peptide Fragments / chemistry*
  • Phosphoproteins / chemistry*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Vesicular Transport Proteins*


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neuropeptides
  • Peptide Fragments
  • Phosphoproteins
  • Proteins
  • STAM protein, human
  • Saccharomyces cerevisiae Proteins
  • TOM1 protein, human
  • VPS27 protein, S cerevisiae
  • Vesicular Transport Proteins
  • epsin
  • hepatocyte growth factor-regulated tyrosine kinase substrate

Associated data

  • PDB/1ELK