2kzt

From Proteopedia

(Difference between revisions)

Revision as of 17:27, 8 November 2023

Structure of the Tandem MA-3 Region of Pdcd4

Structural highlights

2kzt is a 2 chain structure with sequence from Homo sapiens and 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

Function

PDCD4_HUMAN 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 (By similarity).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

One of the key regulatory points of translation initiation is recruitment of the 43S preinitation complex to the 5' mRNA cap by the eIF4F complex (eIF4A, eIF4E, and eIF4G). The tumor suppressor protein Pdcd4 has been shown to inhibit cap-dependent translation by interacting tightly with the RNA helicase eIF4A via its tandem MA-3 domains. The NMR studies reported here reveal a fairly extensive and well defined interface between the two MA-3 domains in solution, which appears to be stabilized by a network of interdomain salt bridges and hydrogen bonds, and reveals a unique orientation of the two domains. Characterization of the stoichiometry of the Pdcd4-eIF4A complex suggests that under physiological conditions Pdcd4 binds to a single molecule of eIF4A, which involves contacts with both Pdcd4 MA-3 domains. We also show that contacts mediated by a conserved acidic patch on the middle MA-3 domain of Pdcd4 are essential for forming a tight complex with eIF4A in vivo, whereas the equivalent region of the C-terminal MA-3 domain appears to have no role in complex formation in vivo. The formation of a 1:1 eIF4A-Pdcd4 complex in solution is consistent with the reported presence in vivo of only one molecule of eIF4A in the eIF4F complex. Pdcd4 has also been reported to interact directly with the middle region of eIF4G, however, we were unable to obtain any evidence for even a weak, transient direct interaction.

Structure of the tandem MA-3 region of Pdcd4 protein and characterization of its interactions with eIF4A and eIF4G: molecular mechanisms of a tumor suppressor.,Waters LC, Strong SL, Ferlemann E, Oka O, Muskett FW, Veverka V, Banerjee S, Schmedt T, Henry AJ, Klempnauer KH, Carr MD J Biol Chem. 2011 May 13;286(19):17270-80. Epub 2011 Mar 16. PMID:21454508^[7]

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

References

↑ Palamarchuk A, Efanov A, Maximov V, Aqeilan RI, Croce CM, Pekarsky Y. Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. Cancer Res. 2005 Dec 15;65(24):11282-6. PMID:16357133 doi:10.1158/0008-5472.CAN-05-3469
↑ Yang HS, Matthews CP, Clair T, Wang Q, Baker AR, Li CC, Tan TH, Colburn NH. Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion. Mol Cell Biol. 2006 Feb;26(4):1297-306. PMID:16449643 doi:26/4/1297
↑ Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science. 2006 Oct 20;314(5798):467-71. PMID:17053147 doi:10.1126/science.1130276
↑ Suzuki C, Garces RG, Edmonds KA, Hiller S, Hyberts SG, Marintchev A, Wagner G. PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains. Proc Natl Acad Sci U S A. 2008 Feb 22;. PMID:18296639
↑ Loh PG, Yang HS, Walsh MA, Wang Q, Wang X, Cheng Z, Liu D, Song H. Structural basis for translational inhibition by the tumour suppressor Pdcd4. EMBO J. 2009 Feb 4;28(3):274-85. Epub 2009 Jan 15. PMID:19153607 doi:10.1038/emboj.2008.278
↑ Chang JH, Cho YH, Sohn SY, Choi JM, Kim A, Kim YC, Jang SK, Cho Y. Crystal structure of the eIF4A-PDCD4 complex. Proc Natl Acad Sci U S A. 2009 Feb 9. PMID:19204291
↑ Waters LC, Strong SL, Ferlemann E, Oka O, Muskett FW, Veverka V, Banerjee S, Schmedt T, Henry AJ, Klempnauer KH, Carr MD. Structure of the tandem MA-3 region of Pdcd4 protein and characterization of its interactions with eIF4A and eIF4G: molecular mechanisms of a tumor suppressor. J Biol Chem. 2011 May 13;286(19):17270-80. Epub 2011 Mar 16. PMID:21454508 doi:10.1074/jbc.M110.166157

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kzt"

@@ Line 1: / Line 1: @@
 ==Structure of the Tandem MA-3 Region of Pdcd4==
-<StructureSection load='2kzt' size='340' side='right'caption='[[2kzt]], [[NMR_Ensembles_of_Models | 73 NMR models]]' scene=''>
+<StructureSection load='2kzt' size='340' side='right'caption='[[2kzt]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2kzt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KZT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2kzt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KZT FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kzt OCA], [https://pdbe.org/2kzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kzt RCSB], [https://www.ebi.ac.uk/pdbsum/2kzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kzt ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kzt OCA], [https://pdbe.org/2kzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kzt RCSB], [https://www.ebi.ac.uk/pdbsum/2kzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kzt ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[https://www.uniprot.org/uniprot/PDCD4_MOUSE PDCD4_MOUSE]] Note=Decreases benign tumor development and malignant progression.
 == Function ==
-[[https://www.uniprot.org/uniprot/PDCD4_HUMAN PDCD4_HUMAN]] 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 (By similarity).<ref>PMID:16357133</ref> <ref>PMID:16449643</ref> <ref>PMID:17053147</ref> <ref>PMID:18296639</ref> <ref>PMID:19153607</ref> <ref>PMID:19204291</ref>  [[https://www.uniprot.org/uniprot/PDCD4_MOUSE 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.<ref>PMID:12482958</ref> <ref>PMID:12894233</ref> <ref>PMID:16024603</ref> <ref>PMID:17060447</ref>
+[https://www.uniprot.org/uniprot/PDCD4_HUMAN PDCD4_HUMAN] 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 (By similarity).<ref>PMID:16357133</ref> <ref>PMID:16449643</ref> <ref>PMID:17053147</ref> <ref>PMID:18296639</ref> <ref>PMID:19153607</ref> <ref>PMID:19204291</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Banerjee, S]]
+[[Category: Banerjee S]]
-[[Category: Carr, M D]]
+[[Category: Carr MD]]
-[[Category: Henry, A J]]
+[[Category: Henry AJ]]
-[[Category: Klempnauer, K H]]
+[[Category: Klempnauer KH]]
-[[Category: Muskett, F W]]
+[[Category: Muskett FW]]
-[[Category: Oka, O]]
+[[Category: Oka O]]
-[[Category: Schmedt, T]]
+[[Category: Schmedt T]]
-[[Category: Strong, S L]]
+[[Category: Strong SL]]
-[[Category: Veverka, V]]
+[[Category: Veverka V]]
-[[Category: Waters, L C]]
+[[Category: Waters LC]]
-[[Category: Apoptosis]]
-[[Category: Eif4a]]
-[[Category: Heat]]
-[[Category: Ma-3]]
-[[Category: Pdcd4]]

2kzt

From Proteopedia

Revision as of 17:27, 8 November 2023

Structure of the Tandem MA-3 Region of Pdcd4

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox