6KAL

Crystal structure of FKRP in complex with Mg ion and CMP

Summary for 6KAL

• Entry DOI: 10.2210/pdb6kal/pdb
• Descriptor: Fukutin-related protein, ZINC ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: glycosyltranferase, phospho ribitoyl tranferase, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 203404.54

Authors

Kuwabara, N. (deposition date: 2019-06-23, release date: 2020-01-15, Last modification date: 2020-07-29)

Primary citation

Kuwabara, N.,Imae, R.,Manya, H.,Tanaka, T.,Mizuno, M.,Tsumoto, H.,Kanagawa, M.,Kobayashi, K.,Toda, T.,Senda, T.,Endo, T.,Kato, R.
Crystal structures of fukutin-related protein (FKRP), a ribitol-phosphate transferase related to muscular dystrophy.
Nat Commun, 11:303-303, 2020

PubMed Abstract: α-Dystroglycan (α-DG) is a highly-glycosylated surface membrane protein. Defects in the O-mannosyl glycan of α-DG cause dystroglycanopathy, a group of congenital muscular dystrophies. The core M3 O-mannosyl glycan contains tandem ribitol-phosphate (RboP), a characteristic feature first found in mammals. Fukutin and fukutin-related protein (FKRP), whose mutated genes underlie dystroglycanopathy, sequentially transfer RboP from cytidine diphosphate-ribitol (CDP-Rbo) to form a tandem RboP unit in the core M3 glycan. Here, we report a series of crystal structures of FKRP with and without donor (CDP-Rbo) and/or acceptor [RboP-(phospho-)core M3 peptide] substrates. FKRP has N-terminal stem and C-terminal catalytic domains, and forms a tetramer both in crystal and in solution. In the acceptor complex, the phosphate group of RboP is recognized by the catalytic domain of one subunit, and a phosphate group on O-mannose is recognized by the stem domain of another subunit. Structure-based functional studies confirmed that the dimeric structure is essential for FKRP enzymatic activity.

PubMed: 31949166
DOI: 10.1038/s41467-019-14220-z

Experimental method

X-RAY DIFFRACTION (2.6 Å)