Carbohydrate and domain architecture of an immature antibody glycoform exhibiting enhanced effector functions.
Antibodies contain a conserved glycosylation site that has emerged as a target for the modulation of antibody effector functions. The crystal structure of a biosynthetic intermediate of human IgG1, bearing immature oligomannose-type glycans and reported to display increased antibody-dependent cellular cytotoxicity, demonstrates that glycan engineering can bias the Fc to an open conformation primed for receptor binding.
Crispin
Max
M
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
Bowden
Thomas A
TA
Coles
Charlotte H
CH
Harlos
Karl
K
Aricescu
A Radu
AR
Harvey
David J
DJ
Stuart
David I
DI
Jones
E Yvonne
EY
D000920:Antibody-Dependent Cell Cytotoxicity; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055672:Static Electricity
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D009844:Oligosaccharides; D011994:Recombinant Proteins; C028569:oligomannoside