Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments.
HIV-1 antibody
antibody engineering
antibody-membrane interaction
aromatic grafting
membrane biophysics
protein-membrane interaction
site-selective chemical modification
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
18 08 2020
18 08 2020
Historique:
received:
04
05
2020
revised:
02
07
2020
accepted:
23
07
2020
entrez:
20
8
2020
pubmed:
20
8
2020
medline:
29
5
2021
Statut:
ppublish
Résumé
The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes.
Identifiants
pubmed: 32814041
pii: S2211-1247(20)31022-6
doi: 10.1016/j.celrep.2020.108037
pmc: PMC7861656
mid: NIHMS1663757
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Membrane Lipids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108037Subventions
Organisme : Wellcome Trust
ID : 107457/Z/15/Z
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI143563
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12010/UNIT PROGRAMS G0902418
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12025
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/9
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/9
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests A patent application covering several aspects of this work has been filled by Kyushu University/UPV-EHU/CSIC/FBB, listing E.R., R.S.-E., A.O., J.L.N., and J.M.M.C. as inventors.
Références
Nat Commun. 2019 Nov 26;10(1):5389
pubmed: 31772165
Nat Protoc. 2010 Jun;5(6):1033-41
pubmed: 20539279
J Virol. 1994 Nov;68(11):7433-47
pubmed: 7933127
J Virol. 2003 Jun;77(12):6965-78
pubmed: 12768015
J Am Chem Soc. 2019 May 22;141(20):8005-8013
pubmed: 30974939
Cell Rep. 2020 Apr 28;31(4):107583
pubmed: 32348769
Nat Chem. 2016 Feb;8(2):103-13
pubmed: 26791892
Virology. 2008 Aug 1;377(2):364-78
pubmed: 18539308
PLoS Pathog. 2017 Feb 22;13(2):e1006212
pubmed: 28225819
Nat Struct Biol. 1996 Oct;3(10):842-8
pubmed: 8836100
FEBS Lett. 2011 Nov 16;585(22):3533-7
pubmed: 22020218
Cell. 2020 Jun 25;181(7):1695
pubmed: 32589960
Cancer Cell. 2018 Nov 12;34(5):792-806.e5
pubmed: 30449325
Biophys J. 2005 Mar;88(3):1818-27
pubmed: 15596514
Mol Cell. 2000 Nov;6(5):1233-42
pubmed: 11106760
Cell Host Microbe. 2019 Nov 13;26(5):623-637.e8
pubmed: 31653484
J Virol. 2009 Jul;83(14):7337-48
pubmed: 19439467
Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905
pubmed: 12019106
J Biol Chem. 2016 Aug 12;291(33):16948-62
pubmed: 27311714
AIDS Res Hum Retroviruses. 2001 Dec 10;17(18):1757-65
pubmed: 11788027
Nature. 2012 Nov 15;491(7424):406-12
pubmed: 23151583
Sci Immunol. 2017 Jan 27;2(7):
pubmed: 28783671
MAbs. 2019 Feb/Mar;11(2):265-296
pubmed: 30526315
Biochim Biophys Acta. 2013 Mar;1828(3):1094-101
pubmed: 23274277
J Virol. 2015 Dec;89(23):11975-89
pubmed: 26378169
PLoS Pathog. 2013 Feb;9(2):e1003184
pubmed: 23468626
Nat Rev Immunol. 2018 May;18(5):297-308
pubmed: 29379211
Nat Rev Drug Discov. 2017 Sep;16(9):787-810
pubmed: 28706220
Sci Rep. 2016 Dec 01;6:38177
pubmed: 27905530
J Comput Chem. 2005 Dec;26(16):1781-802
pubmed: 16222654
J Virol. 2010 Apr;84(7):3382-95
pubmed: 20089658
J Phys Chem B. 1998 Apr 30;102(18):3586-616
pubmed: 24889800
J Comput Chem. 2008 Aug;29(11):1859-65
pubmed: 18351591
Annu Rev Biophys Biomol Struct. 1999;28:319-65
pubmed: 10410805
Science. 2016 Mar 4;351(6277):1043-8
pubmed: 26941313
J Biol Chem. 2017 Mar 31;292(13):5571-5583
pubmed: 28213514
Nature. 2003 Mar 20;422(6929):307-12
pubmed: 12646921
Biochemistry. 1998 Oct 20;37(42):14713-8
pubmed: 9778346
Immunity. 2019 Mar 19;50(3):677-691.e13
pubmed: 30876875
Anal Sci. 2019 Jan 10;35(1):5-27
pubmed: 30318491
Nat Commun. 2019 Jan 8;10(1):78
pubmed: 30622256
MAbs. 2013 Jan-Feb;5(1):22-33
pubmed: 23211638
J Phys Chem B. 2010 Jun 17;114(23):7830-43
pubmed: 20496934
Cell Metab. 2019 Mar 5;29(3):611-626.e5
pubmed: 30581119
J Am Chem Soc. 2016 Jun 29;138(25):7946-50
pubmed: 27254476
Int Rev Cell Mol Biol. 2017;331:289-383
pubmed: 28325214
Immunity. 2016 Jan 19;44(1):21-31
pubmed: 26777395
Science. 2014 Nov 7;346(6210):759-63
pubmed: 25298114
Cell Rep. 2018 Feb 13;22(7):1798-1809
pubmed: 29444432
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5525-30
pubmed: 18378908
J Virol. 2001 Dec;75(24):12198-208
pubmed: 11711611
J Biol Chem. 2001 Aug 31;276(35):32395-8
pubmed: 11432876
Sci Rep. 2016 Sep 28;6:34190
pubmed: 27678107
J Virol. 2018 Mar 28;92(8):
pubmed: 29386285
Nat Biotechnol. 2005 Oct;23(10):1289-93
pubmed: 16170312
Biochemistry. 1998 Oct 13;37(41):14563-74
pubmed: 9772185
Nat Microbiol. 2018 Jun;3(6):670-677
pubmed: 29736037