7E9L

Crystal Structure of POMGNT2 in complex with UDP and mono-mannosyl peptide (379Man short peptide)

7E9L の概要

• エントリーDOI: 10.2210/pdb7e9l/pdb
• 分子名称: Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2, mono-mannosyl peptide (379Man short peptide), 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: glycosyltransferase, o-mannose type glycosylation, transferase
• 由来する生物種: Bos taurus (Bovine); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 127102.40

構造登録者

Kuwabara, N. (登録日: 2021-03-04, 公開日: 2021-05-05, 最終更新日: 2024-10-16)

主引用文献

Imae, R.,Kuwabara, N.,Manya, H.,Tanaka, T.,Tsuyuguchi, M.,Mizuno, M.,Endo, T.,Kato, R.
The structure of POMGNT2 provides new insights into the mechanism to determine the functional O-mannosylation site on alpha-dystroglycan.
Genes Cells, 26:485-494, 2021

PubMed Abstract: Defects in the O-mannosyl glycan of α-dystroglycan (α-DG) are associated with α-dystroglycanopathy, a group of congenital muscular dystrophies. While α-DG has many O-mannosylation sites, only the specific positions can be modified with the functional O-mannosyl glycan, namely, core M3-type glycan. POMGNT2 is a glycosyltransferase which adds β1,4-linked GlcNAc to the O-mannose (Man) residue to acquire core M3-type glycan. Although it is assumed that POMGNT2 extends the specific O-Man residues around particular amino acid sequences, the details are not well understood. Here, we determined a series of crystal structures of POMGNT2 with and without the acceptor O-mannosyl peptides and identified the critical interactions between POMGNT2 and the acceptor peptide. POMGNT2 has an N-terminal catalytic domain and a C-terminal fibronectin type III (FnIII) domain and forms a dimer. The acceptor peptide is sandwiched between the two protomers. The catalytic domain of one protomer recognizes the O-mannosylation site (TPT motif), and the FnIII domain of the other protomer recognizes the C-terminal region of the peptide. Structure-based mutational studies confirmed that amino acid residues of the catalytic domain interacting with mannose or the TPT motif are essential for POMGNT2 enzymatic activity. In addition, the FnIII domain is also essential for the activity and it interacts with the peptide mainly by hydrophobic interaction. Our study provides the first atomic-resolution insights into specific acceptor recognition by the FnIII domain of POMGNT2. The catalytic mechanism of POMGNT2 is proposed based on the structure.

PubMed: 33893702
DOI: 10.1111/gtc.12853

実験手法

X-RAY DIFFRACTION (2.1 Å)