2hm8

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Solution Structure of the C-terminal MA-3 domain of Pdcd4

Structural highlights

2hm8 is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PDCD4_MOUSE Note=Decreases benign tumor development and malignant progression.

Function

PDCD4_MOUSE Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA.[1] [2] [3] [4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Programmed cell death protein 4 (Pdcd4) is a novel tumour suppressor protein, which is involved in the control of eukaryotic transcription and translation. The regulation of translation involves specific interactions with eukaryotic initiation factor (eIF)4A and eIF4G, which are mediated via the two tandem MA-3 domains. We have determined the structure of the C-terminal MA-3 domain of Pdcd4 (Pdcd4 MA-3(C)), characterized its interaction with eIF4A and compared the features of nuclear magnetic resonance (NMR) spectra obtained from the single domain and tandem MA-3 region. Pdcd4 MA-3(C) is composed of three layers of helix-turn-helix hairpins capped by a single helix and shows close structural homology to the atypical HEAT repeats found in many eIFs. The sequence conservation and NMR data strongly suggest that the tandem MA-3 region is composed of two equivalent domains connected by a somewhat flexible linker. Pdcd4 MA-3(C) was found to interact with the N-terminal domain of eIF4A through a conserved surface region encompassing the loop connecting alpha5 and alpha6 and the turn linking alpha3 and alpha4. This site is strongly conserved in other MA-3 domains known to interact with eIF4A, including the preceding domain of Pdcd4, suggesting a common mode of binding.

Structure of the C-terminal MA-3 domain of the tumour suppressor protein Pdcd4 and characterization of its interaction with eIF4A.,Waters LC, Veverka V, Bohm M, Schmedt T, Choong PT, Muskett FW, Klempnauer KH, Carr MD Oncogene. 2007 Jul 26;26(34):4941-50. Epub 2007 Feb 19. PMID:17310995[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
3 reviews cite this structure
The tumour suppressor Pdcd4: recent advances in the elucidation of function and regulation.
Lankat-Buttgereit et al. (2009)
2 more
34 other articles
No citations found

See Also

References

  1. ↑ Yang HS, Jansen AP, Komar AA, Zheng X, Merrick WC, Costes S, Lockett SJ, Sonenberg N, Colburn NH. The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. Mol Cell Biol. 2003 Jan;23(1):26-37. PMID:12482958
  2. ↑ Bohm M, Sawicka K, Siebrasse JP, Brehmer-Fastnacht A, Peters R, Klempnauer KH. The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA. Oncogene. 2003 Jul 31;22(31):4905-10. PMID:12894233 doi:10.1038/sj.onc.1206710
  3. ↑ Jansen AP, Camalier CE, Colburn NH. Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis. Cancer Res. 2005 Jul 15;65(14):6034-41. PMID:16024603 doi:65/14/6034
  4. ↑ LaRonde-LeBlanc N, Santhanam AN, Baker AR, Wlodawer A, Colburn NH. Structural basis for inhibition of translation by the tumor suppressor Pdcd4. Mol Cell Biol. 2007 Jan;27(1):147-56. Epub 2006 Oct 23. PMID:17060447 doi:10.1128/MCB.00867-06
  5. ↑ Waters LC, Veverka V, Bohm M, Schmedt T, Choong PT, Muskett FW, Klempnauer KH, Carr MD. Structure of the C-terminal MA-3 domain of the tumour suppressor protein Pdcd4 and characterization of its interaction with eIF4A. Oncogene. 2007 Jul 26;26(34):4941-50. Epub 2007 Feb 19. PMID:17310995

Contents


PDB ID 2hm8

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