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Structural basis of malaria RIFIN binding by LILRB1-containing antibodies
by
Gorman, Jason
, Lanzavecchia, Antonio
, Tan, Joshua
, Zhang, Baoshan
, Xu, Kai
, Crompton, Peter D.
, Tsybovsky, Yaroslav
, Traore, Boubacar
, Geiger, Roger
, Kwong, Peter D.
, Piccoli, Luca
, Daubenberger, Claudia
, Sallusto, Federica
, Silacci-Fregni, Chiara
, Foglierini, Mathilde
, Chen, Yiwei
, Jin, Wenjie
in
13/1
/ 13/106
/ 13/109
/ 13/31
/ 38/1
/ 38/109
/ 38/77
/ 631/250/2152/2153/1291
/ 631/250/2152/2498
/ 631/250/255/1629
/ 82/51
/ 82/58
/ 82/80
/ Adolescent
/ Adult
/ Amino Acid Sequence
/ Analysis
/ Antibodies
/ Antibodies - chemistry
/ Antibodies - immunology
/ Antibodies - ultrastructure
/ Antibody Specificity
/ Antigens
/ Antigens, Protozoan - chemistry
/ Antigens, Protozoan - immunology
/ Antigens, Protozoan - ultrastructure
/ Binding
/ Binding Sites, Antibody
/ Cell receptors
/ Child
/ Child, Preschool
/ Class switching
/ Cohort Studies
/ Composition
/ Cryoelectron Microscopy
/ Deoxyribonucleic acid
/ DNA
/ Domains
/ Elbow
/ Electron microscopy
/ Enzyme binding
/ Fab
/ Genetic aspects
/ Humanities and Social Sciences
/ Humans
/ Identification and classification
/ Immunoglobulins
/ Infant
/ Leukocyte Immunoglobulin-like Receptor B1 - chemistry
/ Leukocyte Immunoglobulin-like Receptor B1 - immunology
/ Malaria
/ Mali
/ Mass spectrometry
/ Mass spectroscopy
/ Microscopy
/ Models, Molecular
/ multidisciplinary
/ Mutation
/ Parasite antigens
/ Phylogenetics
/ Plasmodium falciparum
/ Plasmodium falciparum - chemistry
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Plasmodium falciparum - ultrastructure
/ Polypeptides
/ Protein Domains
/ Receptors
/ Science
/ Science (multidisciplinary)
/ Scientific imaging
/ Structure
/ Surface antigens
/ Vector-borne diseases
/ Viral antibodies
/ Young Adult
2021
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Structural basis of malaria RIFIN binding by LILRB1-containing antibodies
by
Gorman, Jason
, Lanzavecchia, Antonio
, Tan, Joshua
, Zhang, Baoshan
, Xu, Kai
, Crompton, Peter D.
, Tsybovsky, Yaroslav
, Traore, Boubacar
, Geiger, Roger
, Kwong, Peter D.
, Piccoli, Luca
, Daubenberger, Claudia
, Sallusto, Federica
, Silacci-Fregni, Chiara
, Foglierini, Mathilde
, Chen, Yiwei
, Jin, Wenjie
in
13/1
/ 13/106
/ 13/109
/ 13/31
/ 38/1
/ 38/109
/ 38/77
/ 631/250/2152/2153/1291
/ 631/250/2152/2498
/ 631/250/255/1629
/ 82/51
/ 82/58
/ 82/80
/ Adolescent
/ Adult
/ Amino Acid Sequence
/ Analysis
/ Antibodies
/ Antibodies - chemistry
/ Antibodies - immunology
/ Antibodies - ultrastructure
/ Antibody Specificity
/ Antigens
/ Antigens, Protozoan - chemistry
/ Antigens, Protozoan - immunology
/ Antigens, Protozoan - ultrastructure
/ Binding
/ Binding Sites, Antibody
/ Cell receptors
/ Child
/ Child, Preschool
/ Class switching
/ Cohort Studies
/ Composition
/ Cryoelectron Microscopy
/ Deoxyribonucleic acid
/ DNA
/ Domains
/ Elbow
/ Electron microscopy
/ Enzyme binding
/ Fab
/ Genetic aspects
/ Humanities and Social Sciences
/ Humans
/ Identification and classification
/ Immunoglobulins
/ Infant
/ Leukocyte Immunoglobulin-like Receptor B1 - chemistry
/ Leukocyte Immunoglobulin-like Receptor B1 - immunology
/ Malaria
/ Mali
/ Mass spectrometry
/ Mass spectroscopy
/ Microscopy
/ Models, Molecular
/ multidisciplinary
/ Mutation
/ Parasite antigens
/ Phylogenetics
/ Plasmodium falciparum
/ Plasmodium falciparum - chemistry
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Plasmodium falciparum - ultrastructure
/ Polypeptides
/ Protein Domains
/ Receptors
/ Science
/ Science (multidisciplinary)
/ Scientific imaging
/ Structure
/ Surface antigens
/ Vector-borne diseases
/ Viral antibodies
/ Young Adult
2021
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Structural basis of malaria RIFIN binding by LILRB1-containing antibodies
by
Gorman, Jason
, Lanzavecchia, Antonio
, Tan, Joshua
, Zhang, Baoshan
, Xu, Kai
, Crompton, Peter D.
, Tsybovsky, Yaroslav
, Traore, Boubacar
, Geiger, Roger
, Kwong, Peter D.
, Piccoli, Luca
, Daubenberger, Claudia
, Sallusto, Federica
, Silacci-Fregni, Chiara
, Foglierini, Mathilde
, Chen, Yiwei
, Jin, Wenjie
in
13/1
/ 13/106
/ 13/109
/ 13/31
/ 38/1
/ 38/109
/ 38/77
/ 631/250/2152/2153/1291
/ 631/250/2152/2498
/ 631/250/255/1629
/ 82/51
/ 82/58
/ 82/80
/ Adolescent
/ Adult
/ Amino Acid Sequence
/ Analysis
/ Antibodies
/ Antibodies - chemistry
/ Antibodies - immunology
/ Antibodies - ultrastructure
/ Antibody Specificity
/ Antigens
/ Antigens, Protozoan - chemistry
/ Antigens, Protozoan - immunology
/ Antigens, Protozoan - ultrastructure
/ Binding
/ Binding Sites, Antibody
/ Cell receptors
/ Child
/ Child, Preschool
/ Class switching
/ Cohort Studies
/ Composition
/ Cryoelectron Microscopy
/ Deoxyribonucleic acid
/ DNA
/ Domains
/ Elbow
/ Electron microscopy
/ Enzyme binding
/ Fab
/ Genetic aspects
/ Humanities and Social Sciences
/ Humans
/ Identification and classification
/ Immunoglobulins
/ Infant
/ Leukocyte Immunoglobulin-like Receptor B1 - chemistry
/ Leukocyte Immunoglobulin-like Receptor B1 - immunology
/ Malaria
/ Mali
/ Mass spectrometry
/ Mass spectroscopy
/ Microscopy
/ Models, Molecular
/ multidisciplinary
/ Mutation
/ Parasite antigens
/ Phylogenetics
/ Plasmodium falciparum
/ Plasmodium falciparum - chemistry
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Plasmodium falciparum - ultrastructure
/ Polypeptides
/ Protein Domains
/ Receptors
/ Science
/ Science (multidisciplinary)
/ Scientific imaging
/ Structure
/ Surface antigens
/ Vector-borne diseases
/ Viral antibodies
/ Young Adult
2021
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Structural basis of malaria RIFIN binding by LILRB1-containing antibodies
Journal Article
Structural basis of malaria RIFIN binding by LILRB1-containing antibodies
2021
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Overview
Some
Plasmodium falciparum
repetitive interspersed families of polypeptides (RIFINs)—variant surface antigens that are expressed on infected erythrocytes
1
—bind to the inhibitory receptor LAIR1, and insertion of DNA that encodes LAIR1 into immunoglobulin genes generates RIFIN-specific antibodies
2
,
3
. Here we address the general relevance of this finding by searching for antibodies that incorporate LILRB1, another inhibitory receptor that binds to β2 microglobulin and RIFINs through their apical domains
4
,
5
. By screening plasma from a cohort of donors from Mali, we identified individuals with LILRB1-containing antibodies. B cell clones isolated from three donors showed large DNA insertions in the switch region that encodes non-apical LILRB1 extracellular domain 3 and 4 (D3D4) or D3 alone in the variable–constant (VH–CH1) elbow. Through mass spectrometry and binding assays, we identified a large set of RIFINs that bind to LILRB1 D3. Crystal and cryo-electron microscopy structures of a RIFIN in complex with either LILRB1 D3D4 or a D3D4-containing antibody Fab revealed a mode of RIFIN–LILRB1 D3 interaction that is similar to that of RIFIN–LAIR1. The Fab showed an unconventional triangular architecture with the inserted LILRB1 domains opening up the VH–CH1 elbow without affecting VH–VL or CH1–CL pairing. Collectively, these findings show that RIFINs bind to LILRB1 through D3 and illustrate, with a naturally selected example, the general principle of creating novel antibodies by inserting receptor domains into the VH–CH1 elbow.
Plasmodium
antigens called RIFINs bind to specific antibodies that incorporate the inhibitory receptor LILRB1 through its D3 domain, illustrating the principle of receptor-containing antibodies.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/109
/ 13/31
/ 38/1
/ 38/109
/ 38/77
/ 82/51
/ 82/58
/ 82/80
/ Adult
/ Analysis
/ Antigens
/ Antigens, Protozoan - chemistry
/ Antigens, Protozoan - immunology
/ Antigens, Protozoan - ultrastructure
/ Binding
/ Child
/ DNA
/ Domains
/ Elbow
/ Fab
/ Humanities and Social Sciences
/ Humans
/ Identification and classification
/ Infant
/ Leukocyte Immunoglobulin-like Receptor B1 - chemistry
/ Leukocyte Immunoglobulin-like Receptor B1 - immunology
/ Malaria
/ Mali
/ Mutation
/ Plasmodium falciparum - chemistry
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Plasmodium falciparum - ultrastructure
/ Science
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