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TitleThe structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 3314, Year 2022
Publish dateJun 8, 2022
AuthorsL F L Wilson / T Dendooven / S W Hardwick / A Echevarría-Poza / T Tryfona / K B R M Krogh / D Y Chirgadze / B F Luisi / D T Logan / K Mani / P Dupree /
PubMed AbstractHeparan 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 ...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.
External linksNat Commun / PubMed:35676258 / PubMed Central
MethodsEM (single particle)
Resolution2.43 - 2.93 Å
Structure data

11923

7au2

EMDB-11923, PDB-7au2:
Cryo-EM structure of human exostosin-like 3 (EXTL3)
Method: EM (single particle) / Resolution: 2.43 Å

11926

7aua

EMDB-11926, PDB-7aua:
Cryo-EM structure of human exostosin-like 3 (EXTL3) in complex with UDP
Method: EM (single particle) / Resolution: 2.93 Å

Chemicals

ChemComp-MN:
Unknown entry

ChemComp-UDP:
URIDINE-5'-DIPHOSPHATE / UDP*YM / Uridine diphosphate

Source
  • homo sapiens (human)
KeywordsTRANSFERASE / glycosyltransferase / heparan / n-acetylglucosaminyltransferase

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