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  Crystal structure of the human eIF4AIII-CWC22 complex shows how a DEAD-box protein is inhibited by a MIF4G domain

Buchwald, G., Schüssler, S., Basquin, C., Le Hir, H., & Conti, E. (2013). Crystal structure of the human eIF4AIII-CWC22 complex shows how a DEAD-box protein is inhibited by a MIF4G domain. Proceedings of the National Academy of Sciences of the United States of America, 110(48), E4611-E4618. doi:10.1073/pnas.1314684110.

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 Creators:
Buchwald, Gretel1, Author              
Schüssler, Steffen1, Author              
Basquin, Claire1, Author              
Le Hir, Herve2, Author
Conti, Elena1, Author              
Affiliations:
1Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565144              
2external, ou_persistent22              

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Free keywords: EXON JUNCTION COMPLEX; MESSENGER-RNA EXPORT; NONSENSE-MEDIATED DECAY; STRUCTURE PREDICTION; NUCLEOPORIN NUP214; CORE COMPLEX; HELICASES; INITIATION; REVEALS; RECRUITMENThelicase; mRNP; NMD;
 Abstract: DEAD-box proteins are involved in all aspects of RNA processing. They bind RNA in an ATP-dependent manner and couple ATP hydrolysis to structural and compositional rearrangements of ribonucleoprotein particles. Conformational control is a major point of regulation for DEAD-box proteins to act on appropriate substrates and in a timely manner in vivo. Binding partners containing a middle domain of translation initiation factor 4G (MIF4G) are emerging as important regulators. Well-known examples are eIF4G and Gle1, which bind and activate the DEAD-box proteins eIF4A and Dbp5. Here, we report the mechanism of an inhibiting MIF4G domain. We determined the 2.0-angstrom resolution structure of the complex of human eIF4AIII and the MIF4G domain of the splicing factor Complexed With Cef1 (CWC22), an essential prerequisite for exon junction complex assembly by the splicing machinery. The CWC22 MIF4G domain binds both RecA domains of eIF4AIII. The mode of RecA2 recognition is similar to that observed in the activating complexes, yet is specific for eIF4AIII. The way the CWC22 MIF4G domain latches on the eIF4AIII RecA1 domain is markedly different from activating complexes. In the CWC22-eIF4AIII complex, the RNA-binding and ATP-bindingmotifs of the two RecA domains do not face each other, as would be required in the active state, but are in diametrically opposite positions. The binding mode of CWC22 to eIF4AIII reveals a facet of how MIF4G domains use their versatile structural frameworks to activate or inhibit DEAD-box proteins.

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Language(s): eng - English
 Dates: 2013
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000327390400014
DOI: 10.1073/pnas.1314684110
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Abbreviation : PNAS
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 110 (48) Sequence Number: - Start / End Page: E4611 - E4618 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230