The ribosomal stalk is required for ribosome binding, depurination of the rRNA and cytotoxicity of ricin A chain in Saccharomyces cerevisiae.
The ribosomal stalk is required for ribosome binding, depurination of the rRNA and cytotoxicity of ricin A chain in Saccharomyces cerevisiae.
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DOI：
10.1111/j.1365-2958.2008.06492.x
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发表时间：
2008-12
影响因子：
3.6
通讯作者：
Tumer NE
中科院分区：
文献类型：
--
作者：
Chiou JC;Li XP;Remacha M;Ballesta JP;Tumer NE
核糖体失活蛋白（RIPs）如蓖麻毒素、美国商陆抗病毒蛋白（PAP）和志贺样毒素1和2 （Stx1和Stx2）具有相同的底物α-sarcin/ricin环，但它们对原核和真核核糖体的特异性不同。蓖麻毒素对真核核糖体的去嘌呤作用比原核核糖体更有效，而PAP对两种类型的核糖体都有去嘌呤作用。越来越多的证据表明，不同的rip可能使用核糖体上不同的对接位点，这为理解其王国特异性的机制提供了基础。我们之前的研究结果表明，PAP与核糖体蛋白L3结合以去嘌呤α-sarcin/ricin环，并且PAP与L3的结合对其细胞毒性至关重要。在这里，我们使用表面等离子体共振来证明蓖麻毒素A链（RTA）与酿酒酵母核糖体柄的P1和P2蛋白结合。体外RTA处理P蛋白突变体的核糖体比野生型核糖体去嘌呤化程度低。当RTA在ΔP1和ΔP2突变体中表达时，核糖体去嘌呤化减少，这些突变体对RTA的细胞毒性比野生型细胞更有抵抗力。我们进一步发现RTA、Stx1和Stx2对核糖体去嘌呤的要求相似，而PAP对核糖体去嘌呤的要求不同，这证明rip与不同核糖体蛋白的相互作用是其核糖体特异性的原因。
Ribosome inactivating proteins (RIPs) like ricin, pokeweed antiviral protein (PAP) and Shiga-like toxins 1 and 2 (Stx1 and Stx2) share the same substrate, the α-sarcin/ricin loop, but differ in their specificities towards prokaryotic and eukaryotic ribosomes. Ricin depurinates the eukaryotic ribosomes more efficiently than the prokaryotic ribosomes, while PAP can depurinate both types of ribosomes. Accumulating evidence suggests that different docking sites on the ribosome might be used by different RIPs, providing a basis for understanding the mechanism underlying their kingdom specificity. Our previous results demonstrated that PAP binds to the ribosomal protein L3 to depurinate the α-sarcin/ricin loop and binding of PAP to L3 was critical for its cytotoxicity. Here, we used surface plasmon resonance to demonstrate that ricin toxin A chain (RTA) binds to the P1 and P2 proteins of the ribosomal stalk in Saccharomyces cerevisiae. Ribosomes from the P protein mutants were depurinated less than the wild-type ribosomes when treated with RTA in vitro. Ribosome depurination was reduced when RTA was expressed in the ΔP1 and ΔP2 mutants in vivo and these mutants were more resistant to the cytotoxicity of RTA than the wild-type cells. We further show that while RTA, Stx1 and Stx2 have similar requirements for ribosome depurination, PAP has different requirements, providing evidence that the interaction of RIPs with different ribosomal proteins is responsible for their ribosome specificity.
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影响因子：
3.1
作者：
Li, Xiao-Ping;Baricevic, Marianne;Tumer, Nigun E.
通讯作者：
Tumer, Nigun E.
DOI：
10.1046/j.1432-1327.2001.02091.x
发表时间：
2001-04-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Chan, SH;Hung, FSJ;Shaw, PC
通讯作者：
Shaw, PC
通过化学移动扰动和诱变分析，滴虫，核糖体灭活蛋白与核糖体茎蛋白P2之间的相互作用。
影响因子：
14.9
作者：
Chan, Denise S B;Chu, Lai-On;Lee, Ka-Ming;Too, Priscilla H M;Ma, Kit-Wan;Sze, Kong-Hung;Zhu, Guang;Shaw, Pang-Chui;Wong, Kam-Bo
通讯作者：
Wong, Kam-Bo
影响因子：
4.5
作者：
Algire, MA;Maag, D;Lorsch, JR
通讯作者：
Lorsch, JR
DOI：
10.1093/protein/5.8.775
发表时间：
1992-12-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
KIM, Y;ROBERTUS, JD
通讯作者：
ROBERTUS, JD