jp508535f_si_001.pdf (2.46 MB)
Deciphering the Glycosylation Code
journal contribution
posted on 2015-12-17, 04:52 authored by Christopher
R. Ellis, William G. NoidAsparagine-linked carbohydrates profoundly
impact glycoprotein
folding, stability, and structure. However, the “glycosylation
code” that relates these effects to protein sequence remains
unsolved. We report atomically detailed replica exchange molecular
dynamics simulations in explicit solvent that systematically investigate
the impact of glycosylation upon peptides with the central sequon
Pro-Asn-Gly/Ala-Thr-Trp/Ala. These simulations suggest that the effects
of glycosylation may be quite sensitive to steric crowding by the
side chain immediately following the glycosylation site but less sensitive
to stacking interactions with the aromatic Trp residue. In addition,
we compare our simulated ensembles with the known structures for full
length glycoproteins. These structures corroborate the simulations
and also suggest a remarkable consistency between the intraprotein
and protein-glycan interactions of natural glycoproteins. Moreover,
our analysis highlights the significance of left-handed conformations
for compact β-hairpins at glycosylation sites. In summary, these
studies elucidate basic biophysical principles for the glycosylation
code.