Human ribosomal P1-P2 heterodimer represents an optimal docking site for ricin A chain with a prominent role for P1 C-terminus.
Human ribosomal P1-P2 heterodimer represents an optimal docking site for ricin A chain with a prominent role for P1 C-terminus.
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DOI：
10.1038/s41598-017-05675-5
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发表时间：
2017-07-17
影响因子：
4.6
通讯作者：
Tumer NE
中科院分区：
文献类型：
--
作者：
Grela P;Li XP;Horbowicz P;Dźwierzyńska M;Tchórzewski M;Tumer NE
真核生物的P-茎含有两个P1-P2蛋白二聚体，具有保守的C-末端结构域(CTD)，对于与外界因素的相互作用至关重要。为了了解人P1/P2蛋白单个CTD的作用，我们研究了重组人P蛋白复合体和C末端截短形式与蓖麻毒素A链(RTA)的相互作用，RTA结合在茎上以去除sarcin/ricin环(SRL)。用表面等离子激元共振、等温滴定量热法、微尺度热电泳法和生物层干涉法研究了P-蛋白复合体与RTA的相互作用。P2上缺失CTD的P1-P2异源二聚体能够与RTA结合。相反，缺失P1蛋白CTD的P1-P2异源二聚体几乎不与RTA结合。RTA与非截短的P2-P2均二聚体之间的相互作用很小，这表明P1-P2异二聚体的结构对结合RTA是至关重要的。重组的五聚体人秆复合体对RTA的亲和力高于P1-P2二聚体。P1CTD的缺失而不是P2CTD的缺失降低了五聚体与RTA的亲和力。这些结果突显了P1-P2在人类茎五聚体中异二聚体组织的重要性，以及单个P蛋白CTD在与RTA相互作用中功能不对等的重要性。
The eukaryotic P-stalk contains two P1-P2 protein dimers with a conserved C- terminal domain (CTD) critical for the interaction with external factors. To understand the role of the individual CTD of human P1/P2 proteins, we examined the interaction of reconstituted human P-protein complexes and C-terminally truncated forms with ricin A chain (RTA), which binds to the stalk to depurinate the sarcin/ricin loop (SRL). The interaction between P-protein complexes and RTA was examined by surface plasmon resonance, isothermal titration calorimetry, microscale thermophoresis and bio-layer interferometry. The P1-P2 heterodimer missing a CTD on P2 was able to bind RTA. In contrast, the P1-P2 heterodimer missing the CTD of P1 protein displayed almost no binding toward RTA. Very low interaction was detected between RTA and the non-truncated P2-P2 homodimer, suggesting that the structural architecture of the P1-P2 heterodimer is critical for binding RTA. The reconstituted pentameric human stalk complex had higher affinity for RTA than the P1-P2 dimer. Deletion of P1 CTD, but not P2 CTD reduced the affinity of the pentamer for RTA. These results highlight the importance of the heterodimeric organization of P1-P2 in the human stalk pentamer and functional non-equivalence of the individual P-protein CTDs in the interaction with RTA.
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核糖体 P 茎蛋白 P2 与 II 型核糖体失活蛋白蓖麻毒素相互作用的结构见解
影响因子：
4.6
作者：
Fan X;Zhu Y;Wang C;Niu L;Teng M;Li X
通讯作者：
Li X
ricin A链的毒性通过抑制其与核糖体的相互作用来降低。
影响因子：
3.8
作者：
Jetzt, Amanda E.;Li, Xiao-Ping;Tumer, Nilgun E.;Cohick, Wendie S.
通讯作者：
Cohick, Wendie S.
影响因子：
4.5
作者：
Korennykh, Alexei V.;Correll, Carl C.;Piccirilli, Joseph A.
通讯作者：
Piccirilli, Joseph A.
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
影响因子：
3.6
作者：
Chiou JC;Li XP;Remacha M;Ballesta JP;Tumer NE
通讯作者：
Tumer NE