Crystal structure of imaginal disc growth factor-2. A member of a new family of growth-promoting glycoproteins from Drosophila melanogaster.

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TitleCrystal structure of imaginal disc growth factor-2. A member of a new family of growth-promoting glycoproteins from Drosophila melanogaster.
Publication TypeJournal Article
Year of Publication2002
AuthorsVarela, PF, Llera, AS, Mariuzza, RA, Tormo, J
JournalJ Biol Chem
Volume277
Issue15
Pagination13229-36
Date Published2002 Apr 12
ISSN0021-9258
KeywordsAmino Acid Sequence, Animals, Crystallography, X-Ray, Drosophila melanogaster, Drosophila Proteins, Glycoproteins, Models, Molecular, Molecular Sequence Data, Protein Conformation, Sequence Homology, Amino Acid
Abstract

Imaginal 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.

DOI10.1074/jbc.M110502200
Alternate JournalJ. Biol. Chem.
PubMed ID11821393
Grant ListAI 36900 / AI / NIAID NIH HHS / United States