Skip to main content

Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.

Publication ,  Journal Article
Henderson, R; Watts, BE; Ergin, HN; Anasti, K; Parks, R; Xia, S-M; Trama, A; Liao, H-X; Saunders, KO; Bonsignori, M; Wiehe, K; Haynes, BF; Alam, SM
Published in: Nat Commun
February 8, 2019

Somatic mutations within antibody variable and framework regions (FWR) can alter thermostability and structural flexibility, but their impact on functional potency is unclear. Here we study thermostability and use molecular dynamics (MD) simulations to assess the role of FWR mutations during maturation of HIV-1 broadly neutralizing antibodies (bnAbs). The tested bnAbs show lower thermostability than their unmutated ancestor antibodies. FWR mutations in the Fab elbow region are frequently observed in HIV-1 bnAbs and MD simulations show that such FWR mutations alter interdomain flexibility in two HIV-1 bnAbs. In a CD4-binding site lineage, reversion mutations result in a loss of neutralization potency in an early intermediate and affinity-matured bnAb against autologous and heterologous Tier-2 viruses, respectively. Elbow region reversion mutations in a glycan-V3 bnAb modestly reduces potency against an autologous virus isolate. Thus, selection of mutations in the Fab elbow region impacts interdomain conformational flexibility and paratope plasticity during bnAb development.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 8, 2019

Volume

10

Issue

1

Start / End Page

654

Location

England

Related Subject Headings

  • Surface Plasmon Resonance
  • Neutralization Tests
  • Mutation
  • Molecular Dynamics Simulation
  • Humans
  • HIV-1
  • HIV Antibodies
  • Circular Dichroism
  • Calorimetry, Differential Scanning
  • Antibodies, Neutralizing
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Henderson, R., Watts, B. E., Ergin, H. N., Anasti, K., Parks, R., Xia, S.-M., … Alam, S. M. (2019). Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies. Nat Commun, 10(1), 654. https://doi.org/10.1038/s41467-019-08415-7
Henderson, Rory, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, et al. “Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.Nat Commun 10, no. 1 (February 8, 2019): 654. https://doi.org/10.1038/s41467-019-08415-7.
Henderson R, Watts BE, Ergin HN, Anasti K, Parks R, Xia S-M, et al. Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies. Nat Commun. 2019 Feb 8;10(1):654.
Henderson, Rory, et al. “Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.Nat Commun, vol. 10, no. 1, Feb. 2019, p. 654. Pubmed, doi:10.1038/s41467-019-08415-7.
Henderson R, Watts BE, Ergin HN, Anasti K, Parks R, Xia S-M, Trama A, Liao H-X, Saunders KO, Bonsignori M, Wiehe K, Haynes BF, Alam SM. Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies. Nat Commun. 2019 Feb 8;10(1):654.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 8, 2019

Volume

10

Issue

1

Start / End Page

654

Location

England

Related Subject Headings

  • Surface Plasmon Resonance
  • Neutralization Tests
  • Mutation
  • Molecular Dynamics Simulation
  • Humans
  • HIV-1
  • HIV Antibodies
  • Circular Dichroism
  • Calorimetry, Differential Scanning
  • Antibodies, Neutralizing