Sökning: onr:"swepub:oai:lup.lub.lu.se:09ef3b08-9472-4af7-8fb3-a9a8b1413685" >
The structure of EX...
The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis
-
- Wilson, L. F. L. (författare)
- University of Cambridge
-
- Dendooven, T. (författare)
- University of Cambridge
-
- Hardwick, S. W. (författare)
- University of Cambridge
-
visa fler...
-
Echevarría-Poza, A. (författare)
-
Tryfona, T. (författare)
-
- Krogh, K. B. R. M. (författare)
- Novozymes A/S
-
Chirgadze, D. Y. (författare)
-
Luisi, B. F. (författare)
-
- Logan, Derek T (författare)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
-
- Mani, Katrin (författare)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Glycobiology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
-
- Dupree, P. (författare)
- University of Cambridge
-
visa färre...
-
(creator_code:org_t)
- 2022-06-08
- 2022
- Engelska.
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:3314
- Relaterad länk:
-
http://dx.doi.org/10... (free)
-
visa fler...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Wilson, L. F. L.
-
Dendooven, T.
-
Hardwick, S. W.
-
Echevarría-Poza, ...
-
Tryfona, T.
-
Krogh, K. B. R. ...
-
visa fler...
-
Chirgadze, D. Y.
-
Luisi, B. F.
-
Logan, Derek T
-
Mani, Katrin
-
Dupree, P.
-
visa färre...
- Om ämnet
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Biologi
-
och Biokemi och mole ...
- Artiklar i publikationen
-
Nature Communica ...
- Av lärosätet
-
Lunds universitet