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Crystal structure of imaginal disc growth factor-2Crystal structure of imaginal disc growth factor-2
Structural highlights
FunctionIDGF2_DROME Cooperates with insulin-like peptides to stimulate the proliferation, polarization and motility of imaginal disk cells. May act by stabilizing the binding of insulin-like peptides to its receptor through a simultaneous interaction with both molecules to form a multiprotein signaling complex.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedImaginal disc growth factor-2 (IDGF-2) is a member of a recently described family of Drosophila melanogaster-soluble polypeptide growth factors that promote cell proliferation in imaginal discs. Although their precise mode of action has not been established, IDGFs cooperate with insulin in stimulating the growth of imaginal disc cells. We report the crystal structure of IDGF-2 at 1.3-A resolution. The structure shows the classical (betaalpha)(8) barrel-fold of family 18 glycosyl hydrolases, with an insertion of an alpha + beta domain similar to that of Serratia marcescens chitinases A and B. However, amino acid substitutions in the consensus catalytic sequence of chitinases give IDGF-2 a less negatively charged environment in its putative ligand-binding site and preclude the nucleophilic attack mechanism of chitin hydrolysis. Particularly important is the replacement of Glu by Gln at position 132, which has been shown to abolish enzymatic activity in chitinases. Nevertheless, a modest conservation of residues that participate in oligosaccharide recognition suggests that IDGF-2 could bind carbohydrates, assuming several conformational changes to open the partially occluded binding site. Thus, IDGFs may have evolved from chitinases to acquire new functions as growth factors, interacting with cell surface glycoproteins implicated in growth-promoting processes, such as the Drosophila insulin receptor. Crystal structure of imaginal disc growth factor-2. A member of a new family of growth-promoting glycoproteins from Drosophila melanogaster.,Varela PF, Llera AS, Mariuzza RA, Tormo J J Biol Chem. 2002 Apr 12;277(15):13229-36. Epub 2002 Jan 30. PMID:11821393[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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