Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain.
The A4VAR is a variant antigen expressed by a clonal line that binds CD36 and intercellular adhesion molecule-1, ICAM-1. We have cloned and sequenced the extracellular domain coded by the A4var gene. To probe the relationship between A4var expression and parasite adhesion to ICAM-1, var mRNA and pro...
Những tác giả chính: | , , , , , , , |
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Định dạng: | Journal article |
Ngôn ngữ: | English |
Được phát hành: |
1998
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_version_ | 1826297232043802624 |
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author | Smith, J Kyes, S Craig, A Fagan, T Hudson-Taylor, D Miller, L Baruch, D Newbold, C |
author_facet | Smith, J Kyes, S Craig, A Fagan, T Hudson-Taylor, D Miller, L Baruch, D Newbold, C |
author_sort | Smith, J |
collection | OXFORD |
description | The A4VAR is a variant antigen expressed by a clonal line that binds CD36 and intercellular adhesion molecule-1, ICAM-1. We have cloned and sequenced the extracellular domain coded by the A4var gene. To probe the relationship between A4var expression and parasite adhesion to ICAM-1, var mRNA and protein expression were analyzed in an enriched population of A4 parasites that displayed higher ICAM-1 binding. By Northern analyses, A4var was the predominant var message and antisera raised against a recombinant A4VAR protein reacted with the majority of infected erythrocytes, reinforcing previous conclusions that A4VAR binds ICAM-1. A4VAR contains five Duffy-binding like (DBL) domains, and two cysteine-rich interdomain regions (CIDR) domains. DBL and CIDR domains from A4VAR were expressed in mammalian cells to determine which regions mediate binding to CD36 and ICAM-1. Using several different binding assays, the A4VAR CIDR1 was the only domain found to bind CD36. In contrast, the same assays were unable to identify the ICAM-1 binding domain in A4VAR. This is the first time that each of the DBL and CIDR domains from a Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) have been systematically expressed and tested for binding. These results confirm that CIDR1 is sufficient to bind CD36 without any apparent contribution from other domains. |
first_indexed | 2024-03-07T04:28:26Z |
format | Journal article |
id | oxford-uuid:cd77c9dd-5e3c-488f-ab31-77c7cfb5b3d0 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T04:28:26Z |
publishDate | 1998 |
record_format | dspace |
spelling | oxford-uuid:cd77c9dd-5e3c-488f-ab31-77c7cfb5b3d02022-03-27T07:28:53ZAnalysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cd77c9dd-5e3c-488f-ab31-77c7cfb5b3d0EnglishSymplectic Elements at Oxford1998Smith, JKyes, SCraig, AFagan, THudson-Taylor, DMiller, LBaruch, DNewbold, CThe A4VAR is a variant antigen expressed by a clonal line that binds CD36 and intercellular adhesion molecule-1, ICAM-1. We have cloned and sequenced the extracellular domain coded by the A4var gene. To probe the relationship between A4var expression and parasite adhesion to ICAM-1, var mRNA and protein expression were analyzed in an enriched population of A4 parasites that displayed higher ICAM-1 binding. By Northern analyses, A4var was the predominant var message and antisera raised against a recombinant A4VAR protein reacted with the majority of infected erythrocytes, reinforcing previous conclusions that A4VAR binds ICAM-1. A4VAR contains five Duffy-binding like (DBL) domains, and two cysteine-rich interdomain regions (CIDR) domains. DBL and CIDR domains from A4VAR were expressed in mammalian cells to determine which regions mediate binding to CD36 and ICAM-1. Using several different binding assays, the A4VAR CIDR1 was the only domain found to bind CD36. In contrast, the same assays were unable to identify the ICAM-1 binding domain in A4VAR. This is the first time that each of the DBL and CIDR domains from a Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) have been systematically expressed and tested for binding. These results confirm that CIDR1 is sufficient to bind CD36 without any apparent contribution from other domains. |
spellingShingle | Smith, J Kyes, S Craig, A Fagan, T Hudson-Taylor, D Miller, L Baruch, D Newbold, C Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain. |
title | Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain. |
title_full | Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain. |
title_fullStr | Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain. |
title_full_unstemmed | Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain. |
title_short | Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain. |
title_sort | analysis of adhesive domains from the a4var plasmodium falciparum erythrocyte membrane protein 1 identifies a cd36 binding domain |
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