Antigen-Induced Allosteric Changes in a Human IgG1 Fc Increase Low-Affinity Fcγ Receptor Binding

Chiara Orlandi; Daniel Deredge; Krishanu Ray; Neelakshi Gohain; William Tolbert; Anthony L. DeVico; Patrick Wintrode; Marzena Pazgier; George K. Lewis

doi:10.1016/j.str.2020.03.001

Antigen-Induced Allosteric Changes in a Human IgG1 Fc Increase Low-Affinity Fcγ Receptor Binding

Chiara Orlandi, Daniel Deredge, Krishanu Ray, Neelakshi Gohain, William Tolbert, Anthony L. DeVico, Patrick Wintrode, Marzena Pazgier, George K. Lewis^*

^*Corresponding author for this work

Medicine

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Orlandi et al. show that antigen binding to Fab increases binding of IgG1 Fc to low-affinity FcγR by conformational allostery. Leucine to alanine mutations at positions 234 and 235 in the lower hinge of IgG1 globally alter Fc structure and biological activity by configurational allostery.

Original language	English
Pages (from-to)	516-527.e5
Journal	Structure
Volume	28
Issue number	5
DOIs	https://doi.org/10.1016/j.str.2020.03.001
State	Published - 5 May 2020

Keywords

Fc receptor binding
Fc-effector function
HDX-MS
IgG1 LALA variants
RFADCC Assay
antigen binding
configurational allostery
conformational allostery
immunoglobulin

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title = "Antigen-Induced Allosteric Changes in a Human IgG1 Fc Increase Low-Affinity Fcγ Receptor Binding",

abstract = "Orlandi et al. show that antigen binding to Fab increases binding of IgG1 Fc to low-affinity FcγR by conformational allostery. Leucine to alanine mutations at positions 234 and 235 in the lower hinge of IgG1 globally alter Fc structure and biological activity by configurational allostery.",

keywords = "Fc receptor binding, Fc-effector function, HDX-MS, IgG1 LALA variants, RFADCC Assay, antigen binding, configurational allostery, conformational allostery, immunoglobulin",

author = "Chiara Orlandi and Daniel Deredge and Krishanu Ray and Neelakshi Gohain and William Tolbert and DeVico, {Anthony L.} and Patrick Wintrode and Marzena Pazgier and Lewis, {George K.}",

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year = "2020",

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doi = "10.1016/j.str.2020.03.001",

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T1 - Antigen-Induced Allosteric Changes in a Human IgG1 Fc Increase Low-Affinity Fcγ Receptor Binding

AU - Orlandi, Chiara

AU - Deredge, Daniel

AU - Ray, Krishanu

AU - Gohain, Neelakshi

AU - Tolbert, William

AU - DeVico, Anthony L.

AU - Wintrode, Patrick

AU - Pazgier, Marzena

AU - Lewis, George K.

PY - 2020/5/5

Y1 - 2020/5/5

N2 - Orlandi et al. show that antigen binding to Fab increases binding of IgG1 Fc to low-affinity FcγR by conformational allostery. Leucine to alanine mutations at positions 234 and 235 in the lower hinge of IgG1 globally alter Fc structure and biological activity by configurational allostery.

AB - Orlandi et al. show that antigen binding to Fab increases binding of IgG1 Fc to low-affinity FcγR by conformational allostery. Leucine to alanine mutations at positions 234 and 235 in the lower hinge of IgG1 globally alter Fc structure and biological activity by configurational allostery.

KW - Fc receptor binding

KW - Fc-effector function

KW - HDX-MS

KW - IgG1 LALA variants

KW - RFADCC Assay

KW - antigen binding

KW - configurational allostery

KW - conformational allostery

KW - immunoglobulin

UR - http://www.scopus.com/inward/record.url?scp=85082977077&partnerID=8YFLogxK

U2 - 10.1016/j.str.2020.03.001

DO - 10.1016/j.str.2020.03.001

M3 - Article

C2 - 32209433

AN - SCOPUS:85082977077

SN - 0969-2126

VL - 28

SP - 516-527.e5

JO - Structure

JF - Structure

IS - 5

ER -

Antigen-Induced Allosteric Changes in a Human IgG1 Fc Increase Low-Affinity Fcγ Receptor Binding

Abstract

Keywords

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