Distinct reaction mechanisms for hyaluronan biosynthesis in different kingdoms of life.
Glycobiology
; 28(2): 108-121, 2018 02 01.
Article
in En
| MEDLINE
| ID: mdl-29190396
ABSTRACT
Hyaluronan (HA) is an acidic high molecular weight cell surface polysaccharide ubiquitously expressed by vertebrates, some pathogenic bacteria and even viruses. HA modulates many essential physiological processes and is implicated in numerous pathological conditions ranging from autoimmune diseases to cancer. In various pathogens, HA functions as a non-immunogenic surface polymer that reduces host immune responses. It is a linear polymer of strictly alternating glucuronic acid and N-acetylglucosamine units synthesized by HA synthase (HAS), a membrane-embedded family-2 glycosyltransferase. The enzyme synthesizes HA and secretes the polymer through a channel formed by its own membrane-integrated domain. To reveal how HAS achieves these tasks, we determined the biologically functional units of bacterial and viral HAS in a lipid bilayer environment by co-immunoprecipitation, single molecule fluorescence photobleaching, and site-specific cross-linking analyses. Our results demonstrate that bacterial HAS functions as an obligate homo-dimer with two functional HAS copies required for catalytic activity. In contrast, the viral enzyme, closely related to vertebrate HAS, functions as a monomer. Using site-specific cross-linking, we identify the dimer interface of bacterial HAS and show that the enzyme uses a reaction mechanism distinct from viral HAS that necessitates a dimeric assembly.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Viral Proteins
/
Phycodnaviridae
/
Catalytic Domain
/
Hyaluronan Synthases
Limits:
Animals
Language:
En
Journal:
Glycobiology
Journal subject:
BIOQUIMICA
Year:
2018
Document type:
Article
Affiliation country: