Journal
SCIENCE
Volume 327, Issue 5961, Pages 88-92Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1180512
Keywords
-
Categories
Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NCRR NIH HHS [P41 RR018502] Funding Source: Medline
- NIAID NIH HHS [R21 AI055540, R01 AI055540, R01 AI009484-40, R01 AI009484-41, R01 AI009484, R01 AI045927, R01 AI045927-08, AI55540, R01 AI045927-09, R01 AI045927-10] Funding Source: Medline
- NIDDK NIH HHS [P30 DK 54759, P30 DK054759] Funding Source: Medline
- NINDS NIH HHS [U54 NS053672, 1U54NS053672] Funding Source: Medline
- NATIONAL CENTER FOR RESEARCH RESOURCES [P41RR018502] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI055540, R01AI009484, R01AI045927, R01AI055540] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK054759] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [U54NS053672] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Alpha-dystroglycan (alpha-DG) is a cell-surface glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains and certain arenaviruses. Receptor binding is thought to be mediated by a posttranslational modification, and defective binding with laminin underlies a subclass of congenital muscular dystrophy. Using mass spectrometry- and nuclear magnetic resonance (NMR)-based structural analyses, we identified a phosphorylated O-mannosyl glycan on the mucin-like domain of recombinant alpha-DG, which was required for laminin binding. We demonstrated that patients with muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, as well as mice with myodystrophy, commonly have defects in a postphosphoryl modification of this phosphorylated O-linked mannose, and that this modification is mediated by the like-acetylglucosaminyltransferase (LARGE) protein. These findings expand our understanding of the mechanisms that underlie congenital muscular dystrophy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available