BibTex format
@article{Li:2026:10.1038/s41589-025-02113-w,
author = {Li, Z and Chawla, H and Di, Vagno L and Ní, Cheallaigh A and Critcher, M and Sammon, D and Gonzalez-Rodriguez, E and Briggs, DC and Chung, N and Chang, V and Mahoney, KE and Cioce, A and Bineva-Todd, G and Wang, P-Y and Liu, Y-C and Murphy, LD and Chen, Y-H and Narimatsu, Y and Miller, RL and Willems, LI and Malaker, SA and Huang, ML and Miller, GJ and Hohenester, E and Schumann, B},
doi = {10.1038/s41589-025-02113-w},
journal = {Nat Chem Biol},
pages = {612--621},
title = {Xylosyltransferase engineering to manipulate proteoglycans in mammalian cells.},
url = {http://dx.doi.org/10.1038/s41589-025-02113-w},
volume = {22},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Mammalian cells receive signaling instructions through interactions on their surfaces. Proteoglycans are critical to these interactions, carrying long glycosaminoglycans that recruit signaling molecules. Biosynthetic redundancy in the first glycosylation step by two xylosyltransferases XT1/2 complicates annotation of proteoglycans. Here we develop a chemical genetic strategy that manipulates the glycan attachment site of cellular proteoglycans. Through a bump-and-hole tactic, we engineer the two isoenzymes XT1 and XT2 to specifically transfer the chemically tagged xylose analog 6AzGlc to target proteins. The tag contains a bioorthogonal functionality, allowing to visualize and profile target proteins in mammalian cells. Unlike xylose analogs, 6AzGlc is amenable to cellular nucleotide-sugar biosynthesis, establishing the XT1/2 bump-and-hole tactic in cells. The approach allows pinpointing glycosylation sites by mass spectrometry and exploiting the chemical handle to manufacture proteoglycans with defined glycosaminoglycan chains for cellular applications. Engineered XT enzymes permit an orthogonal view into proteoglycan biology through conventional techniques in biochemistry.
AU - Li,Z
AU - Chawla,H
AU - Di,Vagno L
AU - Ní,Cheallaigh A
AU - Critcher,M
AU - Sammon,D
AU - Gonzalez-Rodriguez,E
AU - Briggs,DC
AU - Chung,N
AU - Chang,V
AU - Mahoney,KE
AU - Cioce,A
AU - Bineva-Todd,G
AU - Wang,P-Y
AU - Liu,Y-C
AU - Murphy,LD
AU - Chen,Y-H
AU - Narimatsu,Y
AU - Miller,RL
AU - Willems,LI
AU - Malaker,SA
AU - Huang,ML
AU - Miller,GJ
AU - Hohenester,E
AU - Schumann,B
DO - 10.1038/s41589-025-02113-w
EP - 621
PY - 2026///
SP - 612
TI - Xylosyltransferase engineering to manipulate proteoglycans in mammalian cells.
T2 - Nat Chem Biol
UR - http://dx.doi.org/10.1038/s41589-025-02113-w
UR - https://www.ncbi.nlm.nih.gov/pubmed/41559400
VL - 22
ER -