7AU2

Cryo-EM structure of human exostosin-like 3 (EXTL3)

7AU2 の概要

• エントリーDOI: 10.2210/pdb7au2/pdb
• EMDBエントリー: 11923
• 分子名称: Exostosin-like 3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: glycosyltransferase, heparan, n-acetylglucosaminyltransferase, 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: 205756.40

構造登録者

Wilson, L.F.L.,Dendooven, T.,Hardwick, S.W.,Chirgadze, D.Y.,Luisi, B.F.,Logan, D.T.,Mani, K.,Dupree, P. (登録日: 2020-11-02, 公開日: 2022-05-18, 最終更新日: 2024-11-13)

主引用文献

Wilson, L.F.L.,Dendooven, T.,Hardwick, S.W.,Echevarria-Poza, A.,Tryfona, T.,Krogh, K.B.R.M.,Chirgadze, D.Y.,Luisi, B.F.,Logan, D.T.,Mani, K.,Dupree, P.
The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis.
Nat Commun, 13:3314-3314, 2022

PubMed Abstract: Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism.

PubMed: 35676258
DOI: 10.1038/s41467-022-31048-2

実験手法

ELECTRON MICROSCOPY (2.43 Å)