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人类真核起始因子5（eIF5）和真核起始因子1A（eIF1A）竞争与真核起始因子5B（eIF5B）结合。

Human eIF5 and eIF1A Compete for Binding to eIF5B.

作者信息

Lin Kai Ying, Nag Nabanita, Pestova Tatyana V, Marintchev Assen

机构信息

Department of Physiology & Biophysics , Boston University School of Medicine , Boston , Massachusetts 02118 , United States.

Department of Cell Biology , State University of New York, Downstate Medical Center , Brooklyn , New York 11203 , United States.

出版信息

Biochemistry. 2018 Oct 9;57(40):5910-5920. doi: 10.1021/acs.biochem.8b00839. Epub 2018 Sep 26.

DOI:10.1021/acs.biochem.8b00839
PMID:30211544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6177315/
Abstract

Eukaryotic translation initiation is a multistep process requiring a number of eukaryotic translation initiation factors (eIFs). Two GTPases play key roles in the process. eIF2 brings the initiator Met-tRNA to the preinitiation complex (PIC). Upon start codon selection and GTP hydrolysis promoted by the GTPase-activating protein (GAP) eIF5, eIF2-GDP is displaced from Met-tRNA by eIF5B-GTP and is released in complex with eIF5. eIF5B promotes ribosomal subunit joining, with the help of eIF1A. Upon subunit joining, eIF5B hydrolyzes GTP and is released together with eIF1A. We found that human eIF5 interacts with eIF5B and may help recruit eIF5B to the PIC. An eIF5B-binding motif was identified at the C-terminus of eIF5, similar to that found in eIF1A. Indeed, eIF5 competes with eIF1A for binding and has an ∼100-fold higher affinity for eIF5B. Because eIF5 is the GAP of eIF2, the newly discovered interaction offers a possible mechanism for coordination between the two steps in translation initiation controlled by GTPases: start codon selection and ribosomal subunit joining. Our results indicate that in humans, eIF5B displacing eIF2 from Met-tRNA upon subunit joining may be coupled to eIF1A displacing eIF5 from eIF5B, allowing the eIF5:eIF2-GDP complex to leave the ribosome.

摘要

真核生物的翻译起始是一个多步骤过程，需要多种真核生物翻译起始因子（eIFs）。两种GTP酶在该过程中发挥关键作用。eIF2将起始甲硫氨酰 - tRNA带到起始前复合物（PIC）。在起始密码子选择以及由GTP酶激活蛋白（GAP）eIF5促进的GTP水解后，eIF2 - GDP被eIF5B - GTP从甲硫氨酰 - tRNA上置换下来，并与eIF5形成复合物释放。在eIF1A的帮助下，eIF5B促进核糖体亚基的结合。亚基结合后，eIF5B水解GTP并与eIF1A一起释放。我们发现人类eIF5与eIF5B相互作用，可能有助于将eIF5B招募到PIC。在eIF5的C末端鉴定出一个与eIF1A中相似的eIF5B结合基序。实际上，eIF5与eIF1A竞争结合，并且对eIF5B的亲和力比对eIF1A高约100倍。由于eIF5是eIF2的GAP，新发现的相互作用为GTP酶控制的翻译起始的两个步骤之间的协调提供了一种可能的机制：起始密码子选择和核糖体亚基结合。我们的结果表明，在人类中，亚基结合时eIF5B从甲硫氨酰 - tRNA上置换eIF2可能与eIF1A从eIF5B上置换eIF5偶联，从而使eIF5：eIF2 - GDP复合物离开核糖体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/1f5e0f09280e/nihms-989352-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/c6dea686e6df/nihms-989352-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/a397f51ed6bd/nihms-989352-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/305ec8fc81b8/nihms-989352-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/d0fb8da40e10/nihms-989352-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/1f5e0f09280e/nihms-989352-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/c6dea686e6df/nihms-989352-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/a397f51ed6bd/nihms-989352-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/305ec8fc81b8/nihms-989352-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/d0fb8da40e10/nihms-989352-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c8/6177315/1f5e0f09280e/nihms-989352-f0005.jpg

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Trends Biochem Sci. 2017 Aug;42(8):589-611. doi: 10.1016/j.tibs.2017.03.004. Epub 2017 Apr 22.
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eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling.
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