Structure of Human Guanylate-Binding Protein 1 Representing a Unique Class of GTP-binding Proteins

Nature. 2000 Feb 3;403(6769):567-71. doi: 10.1038/35000617.

Abstract

Interferon-gamma is an immunomodulatory substance that induces the expression of many genes to orchestrate a cellular response and establish the antiviral state of the cell. Among the most abundant antiviral proteins induced by interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2. These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity and an antiviral effect. Here we have determined the crystal structure of full-length human GBP1 to 1.8 A resolution. The amino-terminal 278 residues constitute a modified G domain with a number of insertions compared to the canonical Ras structure, and the carboxy-terminal part is an extended helical domain with unique features. From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • Dynamins
  • Escherichia coli
  • GTP Phosphohydrolases / chemistry
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / genetics
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Sequence Homology, Amino Acid

Substances

  • DNA-Binding Proteins
  • GBP1 protein, human
  • Recombinant Proteins
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Dynamins

Associated data

  • PDB/1DG3