Structural basis of LAIR1 targeting by polymorphic Plasmodium RIFINs.
Antibodies, Protozoan
/ genetics
Antigenic Variation
/ genetics
Antigens, Protozoan
/ immunology
Crystallography, X-Ray
Humans
Malaria, Falciparum
/ immunology
Membrane Proteins
/ immunology
Mutation
Plasmodium falciparum
/ immunology
Protein Domains
/ genetics
Protozoan Proteins
/ immunology
Receptors, Immunologic
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 07 2021
09 07 2021
Historique:
received:
08
02
2021
accepted:
11
06
2021
entrez:
10
7
2021
pubmed:
11
7
2021
medline:
21
7
2021
Statut:
epublish
Résumé
RIFIN, a large family of Plasmodium variant surface antigens, plays a crucial role in malaria pathogenesis by mediating immune suppression through activation of inhibitory receptors such as LAIR1, and antibodies with LAIR1 inserts have been identified that bind infected erythrocytes through RIFIN. However, details of RIFIN-mediated LAIR1 recognition and receptor activation have been unclear. Here, we use negative-stain EM to define the architecture of LAIR1-inserted antibodies and determine crystal structures of RIFIN-variable 2 (V2) domain in complex with a LAIR1 domain. These structures reveal the LAIR1-binding region of RIFIN to be hydrophobic and membrane-distal, to exhibit extensive structural diversity, and to interact with RIFIN-V2 in a one-to-one fashion. Through structural and sequence analysis of various LAIR1 constructs, we identify essential elements of RIFIN-binding on LAIR1. Furthermore, a structure-derived LAIR1-binding sequence signature ascertained >20 LAIR1-binding RIFINs, including some from P. falciparum field strains and Plasmodium species infecting gorillas and chimpanzees.
Identifiants
pubmed: 34244481
doi: 10.1038/s41467-021-24291-6
pii: 10.1038/s41467-021-24291-6
pmc: PMC8270905
doi:
Substances chimiques
Antibodies, Protozoan
0
Antigens, Protozoan
0
Membrane Proteins
0
Protozoan Proteins
0
RIFIN protein, Plasmodium falciparum
0
Receptors, Immunologic
0
leukocyte-associated immunoglobulin-like receptor 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4226Subventions
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AI005023
Pays : United States
Informations de copyright
© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Références
J Struct Biol. 2007 Jan;157(1):38-46
pubmed: 16859925
Mol Biol Evol. 2013 Apr;30(4):772-80
pubmed: 23329690
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Cell Microbiol. 2013 May;15(5):718-26
pubmed: 23351305
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9333-8
pubmed: 10430943
Mol Biol Evol. 2016 Jun;33(6):1635-8
pubmed: 26921390
J Struct Biol. 2007 Jan;157(1):117-25
pubmed: 16828314
Nature. 2016 Jan 7;529(7584):105-109
pubmed: 26700814
Bioinformatics. 2008 Sep 1;24(17):1953-4
pubmed: 18641403
Nature. 2017 Aug 31;548(7669):597-601
pubmed: 28847005
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
J Struct Biol. 1996 Jan-Feb;116(1):190-9
pubmed: 8742743
J Exp Med. 1999 Nov 15;190(10):1393-404
pubmed: 10562315
Blood. 2010 Feb 18;115(7):1364-73
pubmed: 20007810
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9
pubmed: 20457744
Nature. 2020 Nov;587(7833):309-312
pubmed: 32650338
Cell. 2016 Feb 11;164(4):601-2
pubmed: 26871626
Nature. 2010 Sep 23;467(7314):420-5
pubmed: 20864995
Methods Enzymol. 1997;276:307-26
pubmed: 27754618
BMC Genomics. 2009 Sep 21;10:445
pubmed: 19769795
J Struct Biol. 2005 Oct;152(1):36-51
pubmed: 16182563
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Nature. 2017 Dec 7;552(7683):101-105
pubmed: 29186116
Annu Rev Microbiol. 2001;55:673-707
pubmed: 11544371
Nat Med. 2015 Apr;21(4):314-7
pubmed: 25751816
Nucleic Acids Res. 2020 Jul 2;48(W1):W60-W64
pubmed: 32469061
Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
pubmed: 7984417
Nature. 2021 Apr;592(7855):639-643
pubmed: 33790470