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

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-{angstrom} crystal structure of the N-terminal protein core region of the Drosophila glypican Dally-like (Dlp). This structure reveals an elongated, {alpha}-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.

Authors:
; ; ; ;  [1]
  1. Stanford-MED
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
INDUSTRYNIHHHMI
OSTI Identifier:
1021799
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. USA
Additional Journal Information:
Journal Volume: 108; Journal Issue: (32) ; 08, 2011; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; ANIMALS; CELL MEMBRANES; CRYSTAL STRUCTURE; DROSOPHILA; GROWTH FACTORS; PROTEINS; SULFATES

Citation Formats

Kim, Min-Sung, Saunders, Adam M, Hamaoka, Brent Y, Beachy, Philip A, Leahy, Daniel J, and JHU). Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling. United States: N. p., 2011. Web. doi:10.1073/pnas.1109877108.
Kim, Min-Sung, Saunders, Adam M, Hamaoka, Brent Y, Beachy, Philip A, Leahy, Daniel J, & JHU). Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling. United States. https://doi.org/10.1073/pnas.1109877108
Kim, Min-Sung, Saunders, Adam M, Hamaoka, Brent Y, Beachy, Philip A, Leahy, Daniel J, and JHU). 2011. "Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling". United States. https://doi.org/10.1073/pnas.1109877108.
@article{osti_1021799,
title = {Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling},
author = {Kim, Min-Sung and Saunders, Adam M and Hamaoka, Brent Y and Beachy, Philip A and Leahy, Daniel J and JHU)},
abstractNote = {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-{angstrom} crystal structure of the N-terminal protein core region of the Drosophila glypican Dally-like (Dlp). This structure reveals an elongated, {alpha}-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.},
doi = {10.1073/pnas.1109877108},
url = {https://www.osti.gov/biblio/1021799}, journal = {Proc. Natl. Acad. Sci. USA},
issn = {0027-8424},
number = (32) ; 08, 2011,
volume = 108,
place = {United States},
year = {Tue Sep 20 00:00:00 EDT 2011},
month = {Tue Sep 20 00:00:00 EDT 2011}
}