Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling

Min Sung Kim, Adam M. Saunders, Brent Y. Hamaoka, Philip A. Beachy, Daniel J. Leahya

Research output: Contribution to journalArticle

Abstract

Glypicans are heparan sulfate proteoglycans that modulate the signaling of multiple growth factors active during animal development, and loss of glypican function is associated with widespread developmental abnormalities. Glypicans consist of a conserved, approximately 45-kDa N-terminal protein core region followed by a stalk region that is tethered to the cell membrane by a glycosyl- phosphatidylinositol anchor. The stalk regions are predicted to be random coil but contain a variable number of attachment sites for heparan sulfate chains. Both the N-terminal protein core and the heparan sulfate attachments are important for glypican function. We report here the 2.4-Å crystal structure of the N-terminal protein core region of the Drosophila glypican Dally-like (Dlp). This structure reveals an elongated, a-helical fold for glypican core regions that does not appear homologous to any known structure. The Dlp core protein is required for normal responsiveness to Hedgehog (Hh) signals, and we identify a localized region on the Dlp surface important for mediating its function in Hh signaling. Purified Dlp protein core does not, however, interact appreciably with either Hh or an Hh:Ihog complex.

Original languageEnglish (US)
Pages (from-to)13112-13117
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number32
DOIs
StatePublished - Aug 9 2011

ASJC Scopus subject areas

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