Malaria circumsporozoite protein inhibits protein synthesis in mammalian cells

被引:58
作者
Frevert, U [1 ]
Galinski, MR
Hügel, FU
Allon, N
Schreier, H
Smulevitch, S
Shakibaei, M
Clavijo, P
机构
[1] NYU, Sch Med, Dept Med & Mol Parasitol, New York, NY 10010 USA
[2] Adv Therapies Inc, Novato, CA 94949 USA
关键词
circumsporozoite protein; immune evasion; membrane translocation; Plasmodium; protein synthesis;
D O I
10.1093/emboj/17.14.3816
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3816 / 3826
页数:11
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