Structure of a functional IGF2R fragment determined from the anomalous scattering of sulfur.
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).
Brown
James
J
Cancer Research UK Receptor Structure Research Group, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
Esnouf
Robert M
RM
Jones
Margaret A
MA
Linnell
Jane
J
Harlos
Karl
K
Hassan
A Bassim
AB
Jones
E Yvonne
EY
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002645:Chickens / Q000378:metabolism; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000235:genetics; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship
D009363:Neoplasm Proteins; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II