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      Transport mechanisms at the malaria parasite-host cell interface

      review-article
      1 , * , 2 , *
      PLoS Pathogens
      Public Library of Science

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          Abstract

          Obligate intracellular malaria parasites reside within a vacuolar compartment generated during invasion which is the principal interface between pathogen and host. To subvert their host cell and support their metabolism, these parasites coordinate a range of transport activities at this membrane interface that are critically important to parasite survival and virulence, including nutrient import, waste efflux, effector protein export, and uptake of host cell cytosol. Here, we review our current understanding of the transport mechanisms acting at the malaria parasite vacuole during the blood and liver-stages of development with a particular focus on recent advances in our understanding of effector protein translocation into the host cell by the Plasmodium Translocon of EXported proteins (PTEX) and small molecule transport by the PTEX membrane-spanning pore EXP2. Comparison to Toxoplasma gondii and other related apicomplexans is provided to highlight how similar and divergent mechanisms are employed to fulfill analogous transport activities.

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          Most cited references183

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          X-ray structure of a protein-conducting channel.

          A conserved heterotrimeric membrane protein complex, the Sec61 or SecY complex, forms a protein-conducting channel, allowing polypeptides to be transferred across or integrated into membranes. We report the crystal structure of the complex from Methanococcus jannaschii at a resolution of 3.2 A. The structure suggests that one copy of the heterotrimer serves as a functional translocation channel. The alpha-subunit has two linked halves, transmembrane segments 1-5 and 6-10, clamped together by the gamma-subunit. A cytoplasmic funnel leading into the channel is plugged by a short helix. Plug displacement can open the channel into an 'hourglass' with a ring of hydrophobic residues at its constriction. This ring may form a seal around the translocating polypeptide, hindering the permeation of other molecules. The structure also suggests mechanisms for signal-sequence recognition and for the lateral exit of transmembrane segments of nascent membrane proteins into lipid, and indicates binding sites for partners that provide the driving force for translocation.
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            Secretion systems in Gram-negative bacteria: structural and mechanistic insights.

            Bacteria have evolved a remarkable array of sophisticated nanomachines to export various virulence factors across the bacterial cell envelope. In recent years, considerable progress has been made towards elucidating the structural and molecular mechanisms of the six secretion systems (types I-VI) of Gram-negative bacteria, the unique mycobacterial type VII secretion system, the chaperone-usher pathway and the curli secretion machinery. These advances have greatly enhanced our understanding of the complex mechanisms that these macromolecular structures use to deliver proteins and DNA into the extracellular environment or into target cells. In this Review, we explore the structural and mechanistic relationships between these single- and double-membrane-embedded systems, and we briefly discuss how this knowledge can be exploited for the development of new antimicrobial strategies.
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              Importing mitochondrial proteins: machineries and mechanisms.

              Most mitochondrial proteins are synthesized on cytosolic ribosomes and must be imported across one or both mitochondrial membranes. There is an amazingly versatile set of machineries and mechanisms, and at least four different pathways, for the importing and sorting of mitochondrial precursor proteins. The translocases that catalyze these processes are highly dynamic machines driven by the membrane potential, ATP, or redox reactions, and they cooperate with molecular chaperones and assembly complexes to direct mitochondrial proteins to their correct destinations. Here, we discuss recent insights into the importing and sorting of mitochondrial proteins and their contributions to mitochondrial biogenesis.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Pathog
                PLoS Pathog
                plos
                plospath
                PLoS Pathogens
                Public Library of Science (San Francisco, CA USA )
                1553-7366
                1553-7374
                1 April 2021
                April 2021
                : 17
                : 4
                : e1009394
                Affiliations
                [1 ] Department of Biomedical Sciences, Iowa State University, Ames, Iowa, United States of America
                [2 ] Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
                Joan and Sanford I Weill Medical College of Cornell University, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-6196-8689
                https://orcid.org/0000-0003-2132-7320
                Article
                PPATHOGENS-D-20-02719
                10.1371/journal.ppat.1009394
                8016102
                33793667
                543e63fd-f665-4796-bcd6-68664265cd32
                © 2021 Beck, Ho

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Page count
                Figures: 5, Tables: 0, Pages: 27
                Funding
                Funded by: NIH - National Heart, Lung, and Blood Institute
                Award ID: HL133453
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100001024, Roy J. Carver Charitable Trust;
                Award ID: 18-5102
                Award Recipient :
                J.R.B. was supported by grants HL133453 from the NIH and 18-5102 from the Roy J. Carver Charitable Trust ( https://www.carvertrust.org/). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
                Categories
                Review
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cell Membranes
                Membrane Proteins
                Biology and Life Sciences
                Organisms
                Eukaryota
                Protozoans
                Parasitic Protozoans
                Malarial Parasites
                Biology and Life Sciences
                Parasitology
                Parasite Groups
                Apicomplexa
                Plasmodium
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                Red Blood Cells
                Biology and Life Sciences
                Microbiology
                Virology
                Viral Transmission and Infection
                Host Cells
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cell Membranes
                Membrane Proteins
                Integral Membrane Proteins
                Medicine and Health Sciences
                Medical Conditions
                Parasitic Diseases
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cell Membranes

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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