Oligomannose <i>N</i>-Glycans 3D Architecture and Its Response to the Fc?RIIIa Structural Landscape

Oligomannoses are evolutionarily the oldest class of N-glycans, where arms common pentasaccharide unit, i.e., Man?(1–6)-[Man?(1–3)]-Man?(1–4)-GlcNAc?(1–4)-GlcNAc?1-Asn, functionalized exclusively with branched arrangements mannose (Man) monosaccharide units. In mammalian species oligomannose N-glycans can have up to 9 Man; meanwhile structures grow over 200 units in yeast mannan. The highly dynamic nature, branching complexity, and 3D structure oligomannoses been recently highlighted for their roles immune escape infectivity enveloped viruses, such as HIV-1 SARS-CoV2. architectural features that allow these perform functions yet unclear, due intrinsically disordered nature hinders structural characterization. this work we will discuss results 54 ?s cumulative sampling by molecular dynamics (MD) simulations differently processed, free (not protein-linked) vertebrates. We then effects a protein surface on equilibria based 4 MD fully glycosylated CD16a Fc ? receptor (Fc?RIIIa), type glycosylation is known modulate its binding affinity IgG1s, regulating antibody-dependent cellular cytotoxicity (ADCC). Our show protein’s constraints shift conformational ensemble promote conformers satisfy steric requirements hydrogen bonding networks demanded landscape. More importantly, find does not actively distort into populated unlinked forms solution. Ultimately, conformations Man5 linked glycans support experimental evidence high levels hybrid complex at N45 specific presentation N162, which may be involved mediating IgG1 Fc.