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Structural basis for the initiation of glycosaminoglycan biosynthesis by human xylosyltransferase 1

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Title: Structural basis for the initiation of glycosaminoglycan biosynthesis by human xylosyltransferase 1
Authors: Briggs, D
Hohenester, E
Item Type: Journal Article
Abstract: Proteoglycans (PGs) are essential components of the animal extracellular matrix and required for cell adhesion, migration, signalling, and immune function. PGs are composed of a core protein and long glycosaminoglycan (GAG) chains, which often specify PG function. GAG biosynthesis is initiated by peptide O-xylosyltransferases, which transfer xylose onto selected serine residues in the core proteins. We have determined crystal structures of human xylosyltransferase 1 (XT1) in complex with the sugar donor, UDP-xylose, and various acceptor peptides. The structures reveal unique active site features that, in conjunction with functional experiments, explain the substrate specificity of XT1. A constriction within the peptide-binding cleft requires the acceptor serine to be followed by glycine or alanine. The remainder of the cleft can accommodate a wide variety of sequences, but with a general preference for acidic residues. These findings provide a framework for understanding the selectivity of GAG attachment.
Issue Date: 5-Jun-2018
Date of Acceptance: 20-Mar-2018
URI: http://hdl.handle.net/10044/1/58443
DOI: https://dx.doi.org/10.1016/j.str.2018.03.014
ISSN: 0969-2126
Publisher: Elsevier
Start Page: 801
End Page: 809.e3
Journal / Book Title: Structure
Volume: 26
Issue: 6
Copyright Statement: © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Imperial College Trust
Wellcome Trust
Funder's Grant Number: BB/D524840/1
P48895
202926/Z/16/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biophysics
Cell Biology
O-GLCNAC TRANSFERASE
PROTEIN LINKAGE REGION
CRYSTAL-STRUCTURE
FUNCTIONAL-CHARACTERIZATION
XT-II
ENZYME
XYLOSE
XYLT1
PROTEOGLYCANS
MUTATIONS
X-ray crystallography
enzyme catalysis
glycosyltransferase
proteoglycan
06 Biological Sciences
08 Information And Computing Sciences
03 Chemical Sciences
Publication Status: Published
Online Publication Date: 2018-04-19
Appears in Collections:Faculty of Natural Sciences



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