Title : Conformational plasticity of
glycogenin and its maltosaccharide substrate during glycogen biogenesis
Abstract :
- Glycogenin initiates the synthesis of a maltosaccharide chain covalently attached to itself on Tyr195 via a stepwise glucosylation reaction, priming glycogen synthesis
- We have captured crystallographic snapshots of human glycogenin during its reaction cycle, revealing a dynamic conformational switch between ground and active states mediated by the sugar donor UDP-glucose
- This switch includes the ordering of a polypeptide stretch containing Tyr195 , and major movement of an approximately 30-residue "lid" segment covering the active site
- The rearranged lid guides the nascent maltosaccharide chain into the active site in either an intra- or intersubunit mode dependent upon chain length and steric factors and positions the donor and acceptor sugar groups for catalysis
- The Thr83Met mutation, which causes glycogen storage disease XV, is conformationally locked in the ground state and catalytically inactive
- Our data highlight the conformational plasticity of glycogenin and coexistence of two modes of glucosylation as integral to its catalytic mechanism
Output (sent_index, trigger,
protein,
sugar,
site):
- 1. attached, , -, a maltosaccharide chain, Tyr195
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 1. glycogenin, a maltosaccharide chain, Tyr195