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Endothelial protein...
Endothelial protein C receptor binding induces conformational changes to severe malaria-associated group A PfEMP1
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- Rajan Raghavan, Sai Sundar (author)
- Copenhagen University Hospital
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- Turner, Louise (author)
- Copenhagen University Hospital
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- Jensen, Rasmus W. (author)
- Copenhagen University Hospital
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- Johansen, Nicolai Tidemand (author)
- University of Copenhagen
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- Jensen, Daniel Skjold (author)
- Copenhagen University Hospital
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- Gourdon, Pontus (author)
- Lund University,Lunds universitet,Medicinsk strukturbiologi,Forskargrupper vid Lunds universitet,Membranproteinstrukturbiologi,Medical Structural Biology,Lund University Research Groups,Membrane Protein Structural Biology,University of Copenhagen
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- Zhang, Jinqiu (author)
- Zhejiang University
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- Wang, Yong (author)
- Zhejiang University
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- Theander, Thor Grundtvig (author)
- Copenhagen University Hospital
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- Wang, Kaituo (author)
- University of Copenhagen
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- Lavstsen, Thomas (author)
- Copenhagen University Hospital
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Structure. - 0969-2126. ; 31:10, s. 4-1183
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Severe Plasmodium falciparum malaria infections are caused by microvascular sequestration of parasites binding to the human endothelial protein C receptor (EPCR) via the multi-domain P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion ligands. Using cryogenic electron microscopy (Cryo-EM) and PfEMP1 sequence diversity analysis, we found that group A PfEMP1 CIDRα1 domains interact with the adjacent DBLα1 domain through central, conserved residues of the EPCR-binding site to adopt a compact conformation. Upon EPCR binding, the DBLα1 domain is displaced, and the EPCR-binding helix of CIDRα1 is turned, kinked, and twisted to reach a rearranged, stable EPCR-bound conformation. The unbound conformation and the required transition to the EPCR-bound conformation may represent a conformational masking mechanism of immune evasion for the PfEMP1 family.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Rajan Raghavan, ...
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Turner, Louise
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Jensen, Rasmus W ...
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Johansen, Nicola ...
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Jensen, Daniel S ...
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Gourdon, Pontus
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Zhang, Jinqiu
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Wang, Yong
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Theander, Thor G ...
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Wang, Kaituo
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Lavstsen, Thomas
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
- Articles in the publication
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Structure
- By the university
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Lund University