A comparative study of the localization and membrane topology of members of the RIFIN, STEVOR and PfMC-2TM protein families in Plasmodium falciparum-infected erythrocytes
Authors: Judith Anna Marie Scholz
Marthe Janßen
Anna Bachmann
Iris Bruchhaus
Michaela Petter
Egbert Tannich
Mo-Quen Klinkert
Journal: Malaria Journal (2015)
Discipline: CLINICAL MEDICINE
Keywords: Variant surface antigens; Plasmodium falciparum; immune evasion; pathogenicity factors; PfEMP1
Affiliations: Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359, Hamburg, Germany. ., Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359, Hamburg, Germany. ., CRTD/DFG-Center for Regenerative Therapies Dresden, Technical University Dresden, Fetscherstraße 105, 01307, Dresden, Germany. ., Department of Medicine, The Peter Doherty Institute, The University of Melbourne, 792n Elizabeth Street, Melbourne, 3000, VIC, Australia. .

Abstract:  Background: Variant surface antigens (VSA) exposed on the membrane of Plasmodium falciparum infected erythrocytes mediate immune evasion and are important pathogenicity factors in malaria disease. In addition to the well-studied PfEMP1, the small VSA families RIFIN, STEVOR and PfMC-2TM are assumed to play a role in this process. Methods: This study presents a detailed comparative characterization of the localization, membrane topology and extraction profile across the life cycle of various members of these protein families employing confocal microscopy, immunoelectron microscopy and immunoblots. Results: The presented data reveal a clear association of variants of the RIFIN, STEVOR and PfMC-2TM proteins with the host cell membrane and topological studies indicate that the semi-conserved N-terminal region of RIFINs and some STEVOR proteins is exposed at the erythrocyte surface. At the Maurer's clefts, the semi-conserved N-terminal region as well as the variable stretch of RIFINs appears to point to the lumen away from the erythrocyte cytoplasm. These results challenge the previously proposed two transmembrane topology model for the RIFIN and STEVOR protein families and suggest that only one hydrophobic region spans the membrane. In contrast, PfMC-2TM proteins indeed seem to be anchored by two hydrophobic stretches in the host cell membrane exposing just a few, variable amino acids at the surface of the host cell. Conclusion: Together, the host cell surface exposure and topology of RIFIN and STEVOR proteins suggests members of these protein families may indeed be involved in immune evasion of the infected erythrocyte, whereas members of the PfMC-2TM family seem to bear different functions in parasite biology. 

Retracted: No

PubPeer comments:
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 Copy pasted from https: doi.org 10.1016 j.atherosclerosis.2021.06.922 :  Editorial expression of concern: u201cApolipoprotein A-1 binding protein promotes macrophage cholesterol efflux by facilitating apolipoprotein A-1 binding to ABCA1 and preventing ABCA1 degradationu201d [Atherosclerosis volume 248, May 2016, pages 149u2013159]. Published:June 25, 2021. The Editors of Atherosclerosis are issuing an expression of concern to alert readers that credible concerns have been raised regarding the quality of some data in the article above. See also https: retractionwatch.com 2021 07 09 they-seem-to-mean-business-cardiology-journal-flags-papers-cited-hundreds-of-times ,