Structural basis for the synthesis of the core 1 structure by C1GalT1

Andrés Manuel González-Ramírez, Ana Sofia Grosso, Zhang Yang, Ismael Compañón, Helena Coelho, Yoshiki Narimatsu, Henrik Clausen, Filipa Marcelo, Francisco Corzana () and Ramon Hurtado-Guerrero ()
Additional contact information
Andrés Manuel González-Ramírez: Institute of Biocompuation and Physics of Complex Systems, University of Zaragoza
Ana Sofia Grosso: NOVA School of Science and Technology
Zhang Yang: University of Copenhagen
Ismael Compañón: Universidad de La Rioja, Centro de Investigación en Síntesis Química
Helena Coelho: NOVA School of Science and Technology
Yoshiki Narimatsu: University of Copenhagen
Henrik Clausen: University of Copenhagen
Filipa Marcelo: NOVA School of Science and Technology
Francisco Corzana: Universidad de La Rioja, Centro de Investigación en Síntesis Química
Ramon Hurtado-Guerrero: Institute of Biocompuation and Physics of Complex Systems, University of Zaragoza

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract C1GalT1 is an essential inverting glycosyltransferase responsible for synthesizing the core 1 structure, a common precursor for mucin-type O-glycans found in many glycoproteins. To date, the structure of C1GalT1 and the details of substrate recognition and catalysis remain unknown. Through biophysical and cellular studies, including X-ray crystallography of C1GalT1 complexed to a glycopeptide, we report that C1GalT1 is an obligate GT-A fold dimer that follows a SN2 mechanism. The binding of the glycopeptides to the enzyme is mainly driven by the GalNAc moiety while the peptide sequence provides optimal kinetic and binding parameters. Interestingly, to achieve glycosylation, C1GalT1 recognizes a high-energy conformation of the α-GalNAc-Thr linkage, negligibly populated in solution. By imposing this 3D-arrangement on that fragment, characteristic of α-GalNAc-Ser peptides, C1GalT1 ensures broad glycosylation of both acceptor substrates. These findings illustrate a structural and mechanistic blueprint to explain glycosylation of multiple acceptor substrates, extending the repertoire of mechanisms adopted by glycosyltransferases.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29833-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29833-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29833-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().