The crystal structures of the full-length human eukaryotic initiation factor (eIF) 4E complexed with two mRNA cap analogues [7-methylguanosine 5′-triphosphate (m7GTP) and P1-7-methylguanosine-P3-adenosine-5′,5′-triphosphate (m7GpppA)] were determined at 2.0Å resolution (where 1Å = 0.1nm). The flexibility of the C-terminal loop region of eIF4E complexed with m7GTP was significantly reduced when complexed with m7GpppA, suggesting the importance of the second nucleotide in the mRNA cap structure for the biological function of eIF4E, especially the fixation and orientation of the C-terminal loop region, including the eIF4E phosphorylation residue. The present results provide the structural basis for the biological function of both N- and C-terminal mobile regions of eIF4E in translation initiation, especially the regulatory function through the switch-on/off of eIF4E-binding protein—eIF4E phosphorylation.
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March 2002
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Research Article|
March 08 2002
Crystal structures of 7-methylguanosine 5′-triphosphate (m7GTP)- and P1-7-methylguanosine-P3-adenosine-5′,5′-triphosphate (m7GpppA)-bound human full-length eukaryotic initiation factor 4E: biological importance of the C-terminal flexible region
Koji TOMOO;
Koji TOMOO
1
∗Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
1To whom correspondence should be addressed (e-mail tomoo@gly.oups.ac.jp).
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Xu SHEN;
Xu SHEN
∗Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
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Koumei OKABE;
Koumei OKABE
∗Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
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Yoshiaki NOZOE;
Yoshiaki NOZOE
∗Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
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Shoichi FUKUHARA;
Shoichi FUKUHARA
∗Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
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Shigenobu MORINO;
Shigenobu MORINO
∗Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
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Toshimasa ISHIDA;
Toshimasa ISHIDA
∗Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
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Taizo TANIGUCHI;
Taizo TANIGUCHI
†Hyogo Institute for Aging Brain and Cognitive Disorders, 520 Saisho-koh, Himeji 670-0981, Japan
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Hiroshi HASEGAWA;
Hiroshi HASEGAWA
†Hyogo Institute for Aging Brain and Cognitive Disorders, 520 Saisho-koh, Himeji 670-0981, Japan
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Akira TERASHIMA;
Akira TERASHIMA
†Hyogo Institute for Aging Brain and Cognitive Disorders, 520 Saisho-koh, Himeji 670-0981, Japan
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Masahiro SASAKI;
Masahiro SASAKI
†Hyogo Institute for Aging Brain and Cognitive Disorders, 520 Saisho-koh, Himeji 670-0981, Japan
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Yoshio KATSUYA;
Yoshio KATSUYA
‡Hyogo Prefectural Institute of Industrial Research, 1479-6 Kanaji, Kamigori-cho, Ako-gun, Hyogo 678-1201, Japan
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Kunihiro KITAMURA;
Kunihiro KITAMURA
§Research Center, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Ohmiya, Saitama 330-0031, Japan
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Hiroshi MIYOSHI;
Hiroshi MIYOSHI
∥Institute for Biomolecular Science, Gakushuin University, Toshima-ku, Tokyo 171-8588, Japan
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Masahide ISHIKAWA;
Masahide ISHIKAWA
∥Institute for Biomolecular Science, Gakushuin University, Toshima-ku, Tokyo 171-8588, Japan
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Kin-ichiro MIURA
Kin-ichiro MIURA
∥Institute for Biomolecular Science, Gakushuin University, Toshima-ku, Tokyo 171-8588, Japan
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Publisher: Portland Press Ltd
Received:
October 18 2001
Revision Received:
January 10 2002
Accepted:
January 17 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 362 (3): 539–544.
Article history
Received:
October 18 2001
Revision Received:
January 10 2002
Accepted:
January 17 2002
Citation
Koji TOMOO, Xu SHEN, Koumei OKABE, Yoshiaki NOZOE, Shoichi FUKUHARA, Shigenobu MORINO, Toshimasa ISHIDA, Taizo TANIGUCHI, Hiroshi HASEGAWA, Akira TERASHIMA, Masahiro SASAKI, Yoshio KATSUYA, Kunihiro KITAMURA, Hiroshi MIYOSHI, Masahide ISHIKAWA, Kin-ichiro MIURA; Crystal structures of 7-methylguanosine 5′-triphosphate (m7GTP)- and P1-7-methylguanosine-P3-adenosine-5′,5′-triphosphate (m7GpppA)-bound human full-length eukaryotic initiation factor 4E: biological importance of the C-terminal flexible region. Biochem J 15 March 2002; 362 (3): 539–544. doi: https://doi.org/10.1042/bj3620539
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