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dc.contributor.authorWilson, LFL
dc.contributor.authorDendooven, T
dc.contributor.authorHardwick, SW
dc.contributor.authorEchevarría-Poza, A
dc.contributor.authorTryfona, T
dc.contributor.authorKrogh, KBRM
dc.contributor.authorChirgadze, Dima
dc.contributor.authorLuisi, Ben
dc.contributor.authorLogan, DT
dc.contributor.authorMani, K
dc.contributor.authorDupree, P
dc.date.accessioned2022-06-09T15:00:24Z
dc.date.available2022-06-09T15:00:24Z
dc.date.issued2022-06-08
dc.date.submitted2021-03-02
dc.identifier.others41467-022-31048-2
dc.identifier.other31048
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337941
dc.descriptionFunder: University of Cambridge; doi: https://doi.org/10.13039/501100000735
dc.descriptionFunder: AstraZeneca; doi: https://doi.org/10.13039/100004325
dc.descriptionFunder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268
dc.descriptionFunder: RCUK | Engineering and Physical Sciences Research Council (EPSRC); doi: https://doi.org/10.13039/501100000266
dc.descriptionFunder: OpenPlant, BB/L014130/1
dc.description.abstractAbstract: 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.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/45/221
dc.subject/631/535/1258/1259
dc.subject/631/45/607
dc.subject/631/45/173
dc.subject/13/106
dc.subject/13/109
dc.subject/82/29
dc.subject/82/80
dc.subject/82/83
dc.subject/82/58
dc.subject/101/28
dc.subjectarticle
dc.titleThe structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis
dc.typeArticle
dc.date.updated2022-06-09T15:00:24Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume13
dc.identifier.doi10.17863/CAM.85347
dcterms.dateAccepted2022-05-31
rioxxterms.versionofrecord10.1038/s41467-022-31048-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidChirgadze, Dima [0000-0001-9942-0993]
dc.contributor.orcidLuisi, Ben [0000-0003-1144-9877]
dc.identifier.eissn2041-1723
pubs.funder-project-idWellcome Trust (Wellcome) (200873/Z/16/Z)
pubs.funder-project-idVetenskapsrådet (Swedish Research Council) (2016-04855, 2014-03402)
pubs.funder-project-idCancerfonden (Swedish Cancer Society) (21 1426 Pj 01 H)


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