{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:56:06Z","timestamp":1790776566836,"version":"4.1.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2,15]]},"abstract":"<jats:p>\n                    Binding of infected erythrocytes to brain venules is a central pathogenic event in the lethal malaria disease complication, cerebral malaria. The only parasite adhesion trait linked to cerebral sequestration is binding to intercellular adhesion molecule-1 (ICAM-1). In this report, we show that\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    erythrocyte membrane protein 1 (PfEMP1) binds ICAM-1. We have cloned and expressed PfEMP1 recombinant proteins from the A4tres parasite. Using heterologous expression in mammalian cells, the minimal ICAM-1 binding domain was a complex domain consisting of the second Duffy binding-like (DBL) domain and the C2 domain. Constructs that contained either domain alone did not bind ICAM-1. Based on phylogenetic criteria, there are five distinct PfEMP1 DBL types designated \u03b1, \u03b2, \u03b3, \u03b4, and \u025b. The DBL domain from the A4tres that binds ICAM-1 is DBL\u03b2 type. A PfEMP1 cloned from a distinct ICAM-1 binding variant, the A4 parasite, contains a DBL\u03b2 domain and a C2 domain in tandem arrangement similar to the A4tres PfEMP1. Anti-PfEMP1 antisera implicate the DBL\u03b2 domain from A4var PfEMP1 in ICAM-1 adhesion. The identification of a\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    ICAM-1 binding domain may clarify mechanisms responsible for the pathogenesis of cerebral malaria and lead to interventions or vaccines that reduce malarial disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.040545897","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"1766-1771","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":191,"title":["Identification of a\n                    <i>Plasmodium falciparum<\/i>\n                    intercellular adhesion molecule-1 binding domain: A parasite adhesion trait implicated in cerebral malaria"],"prefix":"10.1073","volume":"97","author":[{"given":"Joseph D.","family":"Smith","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; 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