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40S核糖体亚基出口通道蛋白uS7/Rps5与真核起始因子2α（eIF2α）之间的相互作用在体内调节起始密码子识别。

Interface between 40S exit channel protein uS7/Rps5 and eIF2α modulates start codon recognition in vivo.

作者信息

Visweswaraiah Jyothsna, Hinnebusch Alan G

机构信息

Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.

出版信息

Elife. 2017 Feb 7;6:e22572. doi: 10.7554/eLife.22572.

DOI:10.7554/eLife.22572
PMID:28169832
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5323038/
Abstract

The eukaryotic pre-initiation complex (PIC) bearing the eIF2·GTP·Met-tRNA ternary complex (TC) scans the mRNA for an AUG codon in favorable context. AUG recognition evokes rearrangement of the PIC from an open, scanning to a closed, arrested conformation. Cryo-EM reconstructions of yeast PICs suggest remodeling of the interface between 40S protein Rps5/uS7 and eIF2α between open and closed states; however, its importance was unknown. uS7 substitutions disrupting eIF2α contacts favored in the open complex increase initiation at suboptimal sites, and uS7-S223D stabilizes TC binding to PICs reconstituted with a UUG start codon, indicating inappropriate rearrangement to the closed state. Conversely, uS7-D215 substitutions, perturbing uS7-eIF2α interaction in the closed state, confer the opposite phenotypes of hyperaccuracy and (for D215L) accelerated TC dissociation from reconstituted PICs. Thus, remodeling of the uS7/eIF2α interface appears to stabilize first the open, and then the closed state of the PIC to promote accurate AUG selection in vivo.

摘要

携带真核起始因子2（eIF2）·鸟苷三磷酸（GTP）·甲硫氨酰转运核糖核酸（Met-tRNA）三元复合物（TC）的真核生物前起始复合物（PIC）会在mRNA上扫描处于合适上下文环境的AUG密码子。AUG识别会引发PIC从开放的扫描构象重排为封闭的停滞构象。酵母PIC的冷冻电镜重建表明，在开放状态和封闭状态之间，40S核糖体蛋白Rps5/uS7与eIF2α之间的界面发生了重塑；然而，其重要性尚不清楚。破坏开放复合物中有利于eIF2α接触的uS7替代物会增加次优位点的起始，并且uS7-S223D会稳定TC与用UUG起始密码子重建的PIC的结合，这表明不恰当地重排为封闭状态。相反，在封闭状态下扰乱uS7-eIF2α相互作用的uS7-D215替代物会产生相反的表型，即超准确性以及（对于D215L而言）加速TC从重建的PIC中解离。因此，uS7/eIF2α界面的重塑似乎首先稳定PIC的开放状态，然后稳定其封闭状态，以促进体内准确的AUG选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/8684fdbae776/elife-22572-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/c6657bce8079/elife-22572-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/8fa30f6e373f/elife-22572-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/3149f11af1a5/elife-22572-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/0e6762d3cf65/elife-22572-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/01864c25429d/elife-22572-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/3e93edea4491/elife-22572-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/0959b088e136/elife-22572-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/af3041049679/elife-22572-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/8684fdbae776/elife-22572-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/c6657bce8079/elife-22572-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/81dcc6598a29/elife-22572-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/3b96e0934a13/elife-22572-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/8fa30f6e373f/elife-22572-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/3149f11af1a5/elife-22572-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/0e6762d3cf65/elife-22572-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/01864c25429d/elife-22572-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/3e93edea4491/elife-22572-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/0959b088e136/elife-22572-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/af3041049679/elife-22572-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ab/5323038/8684fdbae776/elife-22572-resp-fig1.jpg

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