Structure of a functional IGF2R fragment determined from the anomalous scattering of sulfur

EMBO J. 2002 Mar 1;21(5):1054-62. doi: 10.1093/emboj/21.5.1054.

Abstract

Insulin-like growth factor II receptor (IGF2R) is a multifunctional cell surface receptor implicated in tumour suppression. Its growth inhibitory activity has been associated with an ability to bind IGF-II. IGF2R contains 15 homologous extracellular domains, with domain 11 primarily responsible for IGF-II binding. We report a 1.4 A resolution crystal structure of domain 11, solved using the anomalous scattering signal of sulfur. The structure consists of two crossed beta-sheets forming a flattened beta-barrel. Structural analysis identifies the putative IGF-II binding site at one end of the beta-barrel whilst crystal lattice contacts suggest a model for the full-length IGF2R extracellular region. The structure factors and coordinates of IGF2R domain 11 have been deposited in the Protein Data Bank (accession codes 1GP0 and 1GP3).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • Chickens / metabolism
  • Crystallography, X-Ray
  • Evolution, Molecular
  • Humans
  • Insulin-Like Growth Factor II / metabolism
  • Mammals / metabolism
  • Models, Molecular
  • Neoplasm Proteins / genetics
  • Point Mutation
  • Polymorphism, Genetic
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptor, IGF Type 2 / chemistry*
  • Receptor, IGF Type 2 / genetics
  • Receptor, IGF Type 2 / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Structure-Activity Relationship

Substances

  • Neoplasm Proteins
  • Receptor, IGF Type 2
  • Insulin-Like Growth Factor II

Associated data

  • PDB/1E6F
  • PDB/1GP0
  • PDB/1GP3