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2015 ; 2015
(ä): 367579
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Hyaluronan Synthase: The Mechanism of Initiation at the Reducing End and a
Pendulum Model for Polysaccharide Translocation to the Cell Exterior
#MMPMID26472958
Weigel PH
Int J Cell Biol
2015[]; 2015
(ä): 367579
PMID26472958
show ga
Hyaluronan (HA) biosynthesis has been studied for over six decades, but our
understanding of the biochemical details of how HA synthase (HAS) assembles HA is
still incomplete. Class I family members include mammalian and streptococcal
HASs, the focus of this review, which add new intracellular sugar-UDPs at the
reducing end of growing hyaluronyl-UDP chains. HA-producing cells typically
create extracellular HA coats (capsules) and also secrete HA into the surrounding
space. Since HAS contains multiple transmembrane domains and is lipid-dependent,
we proposed in 1999 that it creates an intraprotein HAS-lipid pore through which
a growing HA-UDP chain is translocated continuously across the cell membrane to
the exterior. We review here the evidence for a synthase pore-mediated
polysaccharide translocation process and describe a possible mechanism (the
Pendulum Model) and potential energy sources to drive this ATP-independent
process. HA synthases also synthesize chitin oligosaccharides, which are created
by cleavage of novel oligo-chitosyl-UDP products. The synthesis of chitin-UDP
oligomers by HAS confirms the reducing end mechanism for sugar addition during HA
assembly by streptococcal and mammalian Class I enzymes. These new findings
indicate the possibility that HA biosynthesis is initiated by the ability of HAS
to use chitin-UDP oligomers as self-primers.