PMID- 30213862
OWN - NLM
STAT- MEDLINE
DCOM- 20190321
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 293
IP  - 43
DP  - 2018 Oct 26
TI  - CD16a with oligomannose-type N-glycans is the only "low-affinity" Fc gamma receptor 
      that binds the IgG crystallizable fragment with high affinity in vitro.
PG  - 16842-16850
LID - 10.1074/jbc.RA118.004998 [doi]
AB  - Fc gamma receptors (FcgammaRs) bind circulating IgG (IgG1) at the surface of leukocytes. 
      Antibodies clustered at the surface of a targeted particle trigger a protective 
      immune response through activating FcgammaRs. Three recent reports indicate that the 
      composition of the asparagine-linked carbohydrate chains (N-glycans) of 
      FcgammaRIIIa/CD16a impacted IgG1-binding affinity. Here we determined how N-glycan 
      composition affected the affinity of the "low-affinity" FcgammaRs for six homogeneous 
      IgG1 Fc N-glycoforms (G0, G0F, G2, G2F, A2G2, and A2G2F). Surprisingly, CD16a 
      with oligomannose N-glycans bound to IgG1 Fc (A2G2) with a K(D) = 1.0 +/- 0.1 nm 
      This affinity represents a 51-fold increase over the affinity measured for CD16a 
      with complex-type N-glycans (51 +/- 8 nm) and is comparable with the affinity of 
      FcgammaRI/CD64, the sole "high-affinity" FcgammaR. CD16a N-glycan composition accounted 
      for increases in binding affinity for the other IgG1 Fc glycoforms tested 
      (10-50-fold). This remarkable sensitivity could only be eliminated by preventing 
      glycosylation at Asn(162) with an Asn-to-Gln mutation; mutations at the four 
      other N-glycosylation sites preserved tighter binding in the Man5 glycoform. None 
      of the other low-affinity FcgammaRs showed more than a 3.1-fold increase upon 
      modifying the receptor N-glycan composition, including CD16b, which differs from 
      CD16a by only four amino acid residues. This result indicates that CD16a is 
      unique among the low-affinity FcgammaRs, and modifying only the glycan composition of 
      both the IgG1 Fc ligand and receptor provides a 400-fold range in affinities.
CI  - (c) 2018 Subedi and Barb.
FAU - Subedi, Ganesh P
AU  - Subedi GP
AD  - From the Roy J. Carver Department of Biochemistry, Biophysics and Molecular 
      Biology Iowa State University, Ames, Iowa 50011.
FAU - Barb, Adam W
AU  - Barb AW
AUID- ORCID: 0000-0003-3290-8649
AD  - From the Roy J. Carver Department of Biochemistry, Biophysics and Molecular 
      Biology Iowa State University, Ames, Iowa 50011 abarb@iastate.edu.
LA  - eng
GR  - R01 GM115489/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180913
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (FCGR3A protein, human)
RN  - 0 (FCGR3B protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Oligosaccharides)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, IgG)
RN  - 0 (oligomannoside)
SB  - IM
MH  - GPI-Linked Proteins/metabolism
MH  - Glycosylation
MH  - HEK293 Cells
MH  - Humans
MH  - Immunoglobulin Fc Fragments/*metabolism
MH  - Immunoglobulin G/chemistry/*metabolism
MH  - In Vitro Techniques
MH  - Oligosaccharides/*metabolism
MH  - Polysaccharides/*metabolism
MH  - Protein Binding
MH  - Receptors, IgG/*metabolism
PMC - PMC6204906
OTO - NOTNLM
OT  - Fc receptor
OT  - Fc-gamma receptor
OT  - N-linked glycosylation
OT  - antibody
OT  - post-translational modification (PTM)
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2018/09/15 06:00
MHDA- 2019/03/22 06:00
PMCR- 2019/10/26
CRDT- 2018/09/15 06:00
PHST- 2018/07/20 00:00 [received]
PHST- 2018/08/29 00:00 [revised]
PHST- 2018/09/15 06:00 [pubmed]
PHST- 2019/03/22 06:00 [medline]
PHST- 2018/09/15 06:00 [entrez]
PHST- 2019/10/26 00:00 [pmc-release]
AID - S0021-9258(20)33245-2 [pii]
AID - RA118.004998 [pii]
AID - 10.1074/jbc.RA118.004998 [doi]
PST - ppublish
SO  - J Biol Chem. 2018 Oct 26;293(43):16842-16850. doi: 10.1074/jbc.RA118.004998. Epub 
      2018 Sep 13.