7ZVJ

Homodimeric structure of LARGE1

7ZVJ の概要

• エントリーDOI: 10.2210/pdb7zvj/pdb
• EMDBエントリー: 14985 14987
• 分子名称: Xylosyl- and glucuronyltransferase LARGE1, 2-acetamido-2-deoxy-beta-D-glucopyranose, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: matriglycan, xylose, glucuronic acid, polymerase, transferase., transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 146777.06

構造登録者

Diskin, R.,Katz, M. (登録日: 2022-05-16, 公開日: 2022-11-30, 最終更新日: 2024-10-23)

主引用文献

Katz, M.,Diskin, R.
Structural basis for matriglycan synthesis by the LARGE1 dual glycosyltransferase.
Plos One, 17:e0278713-e0278713, 2022

PubMed Abstract: LARGE1 is a bifunctional glycosyltransferase responsible for generating a long linear polysaccharide termed matriglycan that links the cytoskeleton and the extracellular matrix and is required for proper muscle function. This matriglycan polymer is made with an alternating pattern of xylose and glucuronic acid monomers. Mutations in the LARGE1 gene have been shown to cause life-threatening dystroglycanopathies through the inhibition of matriglycan synthesis. Despite its major role in muscle maintenance, the structure of the LARGE1 enzyme and how it assembles in the Golgi are unknown. Here we present the structure of LARGE1, obtained by a combination of X-ray crystallography and single-particle cryo-EM. We found that LARGE1 homo-dimerizes in a configuration that is dictated by its coiled-coil stem domain. The structure shows that this enzyme has two canonical GT-A folds within each of its catalytic domains. In the context of its dimeric structure, the two types of catalytic domains are brought into close proximity from opposing monomers to allow efficient shuttling of the substrates between the two domains. Together, with putative retention of matriglycan by electrostatic interactions, this dimeric organization offers a possible mechanism for the ability of LARGE1 to synthesize long matriglycan chains. The structural information further reveals the mechanisms in which disease-causing mutations disrupt the activity of LARGE1. Collectively, these data shed light on how matriglycan is synthesized alongside the functional significance of glycosyltransferase oligomerization.

PubMed: 36512577
DOI: 10.1371/journal.pone.0278713

実験手法

X-RAY DIFFRACTION (2.61 Å)