2w97

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Template:STRUCTURE 2w97

Contents

CRYSTAL STRUCTURE OF EIF4E BOUND TO GLYCEROL AND EIF4G1 PEPTIDE

Template:ABSTRACT PUBMED 19440045

Disease

[IF4G1_HUMAN] Defects in EIF4G1 are the cause of Parkinson disease type 18 (PARK18) [MIM:614251]. An autosomal dominant, late-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.[1]

Function

[IF4E_HUMAN] Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.[2] [IF4G1_HUMAN] Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome.

About this Structure

2w97 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Brown CJ, Verma CS, Walkinshaw MD, Lane DP. Crystallization of eIF4E complexed with eIF4GI peptide and glycerol reveals distinct structural differences around the cap-binding site. Cell Cycle. 2009 Jun 15;8(12):1905-11. Epub 2009 Jun 15. PMID:19440045
  1. ↑ Chartier-Harlin MC, Dachsel JC, Vilarino-Guell C, Lincoln SJ, Lepretre F, Hulihan MM, Kachergus J, Milnerwood AJ, Tapia L, Song MS, Le Rhun E, Mutez E, Larvor L, Duflot A, Vanbesien-Mailliot C, Kreisler A, Ross OA, Nishioka K, Soto-Ortolaza AI, Cobb SA, Melrose HL, Behrouz B, Keeling BH, Bacon JA, Hentati E, Williams L, Yanagiya A, Sonenberg N, Lockhart PJ, Zubair AC, Uitti RJ, Aasly JO, Krygowska-Wajs A, Opala G, Wszolek ZK, Frigerio R, Maraganore DM, Gosal D, Lynch T, Hutchinson M, Bentivoglio AR, Valente EM, Nichols WC, Pankratz N, Foroud T, Gibson RA, Hentati F, Dickson DW, Destee A, Farrer MJ. Translation initiator EIF4G1 mutations in familial Parkinson disease. Am J Hum Genet. 2011 Sep 9;89(3):398-406. doi: 10.1016/j.ajhg.2011.08.009. PMID:21907011 doi:10.1016/j.ajhg.2011.08.009
  2. ↑ Tomoo K, Matsushita Y, Fujisaki H, Abiko F, Shen X, Taniguchi T, Miyagawa H, Kitamura K, Miura K, Ishida T. Structural basis for mRNA Cap-Binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods. Biochim Biophys Acta. 2005 Dec 1;1753(2):191-208. Epub 2005 Aug 24. PMID:16271312 doi:10.1016/j.bbapap.2005.07.023

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