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Malaria circumsporozoite protein inhibits protein synthesis in mammalian cells
Native Plasmodium circumsporozoite (CS) protein, translocated by sporozoites into the cytosol of host cells, as well as recombinant CS constructs introduced into the cytoplasm by liposome fusion or transient transfection, all lead to inhibition of protein synthesis in mammalian cells. The following...
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Published in: | The EMBO journal 1998-07, Vol.17 (14), p.3816-3826 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Native
Plasmodium
circumsporozoite (CS) protein, translocated by sporozoites into the cytosol of host cells, as well as recombinant CS constructs introduced into the cytoplasm by liposome fusion or transient transfection, all lead to inhibition of protein synthesis in mammalian cells. The following findings suggest that this inhibition of translation is caused by a binding of the CS protein to ribosomes. (i) The distribution of native CS protein translocated by sporozoites into the cytoplasm as well as microinjected recombinant CS protein suggests association with ribosomes. (ii) Recombinant CS protein binds to RNase‐sensitive sites on rough microsomes. (iii) Synthetic peptides representing the conserved regions I and II‐plus of the
P.falciparum
CS protein displace recombinant CS protein from rough microsomes with dissociation constants in the nanomolar range. (iv) Synthetic peptides representing region I from the
P.falciparum
CS protein and region II‐plus from the
P.falciparum
,
P.berghei
or
P.vivax
CS protein inhibit
in vitro
translation. We propose that
Plasmodium
manipulates hepatocyte protein synthesis to meet the requirements of a rapidly developing schizont. Since macrophages appear to be particularly sensitive to the presence of CS protein in the cytosol, inhibition of translation may represent a novel immune evasion mechanism of
Plasmodium
. |
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ISSN: | 0261-4189 1460-2075 |
DOI: | 10.1093/emboj/17.14.3816 |