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TitleStructural insights into translocation and tailored synthesis of hyaluronan.
Journal, issue, pagesNat Struct Mol Biol, Year 2024
Publish dateSep 25, 2024
AuthorsIreneusz Górniak / Zachery Stephens / Satchal K Erramilli / Tomasz Gawda / Anthony A Kossiakoff / Jochen Zimmer /
PubMed AbstractHyaluronan (HA) is an essential component of the vertebrate extracellular matrix. It is a heteropolysaccharide of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) reaching several megadaltons ...Hyaluronan (HA) is an essential component of the vertebrate extracellular matrix. It is a heteropolysaccharide of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) reaching several megadaltons in healthy tissues. HA is synthesized and translocated in a coupled reaction by HA synthase (HAS). Here, structural snapshots of HAS provide insights into HA biosynthesis, from substrate recognition to HA elongation and translocation. We monitor the extension of a GlcNAc primer with GlcA, reveal the coordination of the uridine diphosphate product by a conserved gating loop and capture the opening of a translocation channel to coordinate a translocating HA polymer. Furthermore, we identify channel-lining residues that modulate HA product lengths. Integrating structural and biochemical analyses suggests an avenue for polysaccharide engineering based on finely tuned enzymatic activity and HA coordination.
External linksNat Struct Mol Biol / PubMed:39322765
MethodsEM (single particle)
Resolution3.2 - 3.4 Å
Structure data

40591

8smm

EMDB-40591, PDB-8smm:
Xenopus laevis hyaluronan synthase 1
Method: EM (single particle) / Resolution: 3.2 Å

40594

8smn

EMDB-40594, PDB-8smn:
Xenopus laevis hyaluronan synthase 1, nascent HA polymer bound state
Method: EM (single particle) / Resolution: 3.2 Å

40598

8smp

EMDB-40598, PDB-8smp:
Xenopus laevis hyaluronan synthase 1, UDP-bound, gating loop inserted state
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-HOH:
WATER

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

ChemComp-MG:
Unknown entry

Source
  • xenopus laevis (African clawed frog)
  • homo sapiens (human)
KeywordsTransferase/Immune System / hyaluronic acid / hyaluronan / HA / HAS / glycosyltransferase / GT / membrane protein / Fab / Transferase-Immune System complex

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