The binding mechanism of eIF2¦Â with its partner proteins, eIF5 and eIF2B¦Å

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• 作者：Zuoqi Gai ; Yumie Kitagawa ; Yoshikazu Tanaka ; Nobutaka Shimizu ; Keisuke Komoda ; Isao Tanaka ; Min Yao
• 关键词：Translation initiation ; Intrinsically disordered domain ; eIF2 ; eIF5 ; eIF2B
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：6 July, 2012
• 年：2012
• 卷：423
• 期：3
• 页码：515-519
• 全文大小：599 K

文摘

The eukaryotic translation initiation factor eIF2 delivers to the ribosomal small subunit in GTP-bound form associated with eIF1, eIF1A, eIF3 and eIF5, and dissociates together with eIF5 as eIF5-eIF2-GDP complex from the ribosomal small subunit after formation of start codon-anticodon base pairing between and mRNA. The inactive form eIF2-GDP is then exchanged for the active form eIF2-GTP by eIF2B for further initiation cycle. Previous studies showed that the C-terminal domains of eIF5 (eIF5-CTD) and eIF2B¦Å (eIF2B¦Å-CTD) have a common eIF2¦Â-binding site for interacting with an N-terminal region of eIF2¦Â (eIF2¦Â-NTD). Here we have reconstructed the complexes of (eIF5-CTD)-(eIF2¦Â-NTD) and (eIF2B¦Å-CTD)-(eIF2¦Â-NTD) in vitro, and investigated binding mechanism by circular dichroism spectroscopy and small angle X-ray scattering in solution. The results showed the conformation of eIF2¦Â-NTD was changed when bound to partner proteins, whereas the structures of eIF5-CTD and eIF2B¦Å-CTD were similar in both isolated and complex states. We propose that eIF2¦Â-NTD works as an intrinsically disordered domain which is disorder in the isolated state, but folds into a definite structure when bound to its partner proteins. Such flexibility of eIF2¦Â-NTD is expected to be responsible for its binding capability.