6qey

From Proteopedia

(Difference between revisions)

Revision as of 06:48, 27 March 2019

IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties

Structural highlights

6qey is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IF2B1_HUMAN] RNA-binding factor that affects mRNA nuclear export, localization, stability and translation. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. Regulates mRNA stability during the integrated cellular stress response (ISR) in stress granules (SGs). Stabilizes the BTRC/FBW1A mRNA from degradation by disrupting miRNA-dependent interaction with AGO2. Identified in a HCV IRES-mediated translation complex, that enhances translation at the Hepatitis C virus (HCV) RNA-replicon via the internal ribosome entry site (IRES), but does not affect 5'cap-dependent translation. Acts as a HIV-1 retrovirus restriction factor that reduces HIV-1 assembly by inhibiting viral RNA packaging, assembly and processing of HIV-1 GAG protein on cellular membranes. Binds to mRNAs in stress granules (SGs). Binds to the stem-loop IV of the 5'-UTR and to the variable region and the poly(U-C) motif of the 3'-UTR of the HCV RNA-replicon. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulates its subcellular localization and translation. Binds both to the coding region mRNA stability determinant (CRD) and to AU-rich sequences in the 3'-UTR of the MYC and CD44 mRNAs and stabilizes these mRNAs. Binds to the fourth and fifth exons of the oncofetal H19 and neuron-specific TAU mRNAs and regulates their localizations. Binds to the adenine-rich autoregulatory sequence (ARS) 5'-UTR of the PABPC1 mRNA and is involved in its translational repression. The RNA-binding activity to ARS is stimulated by PABPC1. Binds to the coding sequence region of BTRC/FBW1A mRNA and mediates stabilization of BTRC/FBW1A and MYC mRNAs in response to beta-catenin signaling. Binding to RNA employs a cooperative, sequential mechanism of homo- or heterodimerisation. Also involved in growth or survival of lung-cancer cells. Protects the MYC and MDR-1 mRNAs from cleavage by a endoribonuclease, thus prolonging their stabilities (By similarity). Binds to the 3'-UTR axonal localization signal (ALS) of TAU mRNA (By similarity). Binds to a conserved 54-nucleotide element in the 3'-UTR of the beta actin mRNA known as the 'zipcode' (By similarity). Promotes translocation of the beta-actin mRNA to dendrites (By similarity). May act as a regulator of mRNA transport to activated synapses in response to synaptic activity (By similarity).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15]

Publication Abstract from PubMed

IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit. Importantly, the high-affinity RNA-binding by KH1KH2 is achieved by an inter-domain coupling 50-fold stronger than that existing in a second pseudo-dimer in the protein, KH3KH4. The presence of this strong coupling supports a role of RNA re-modelling in IMP1 recognition of known cancer targets.

IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.,Dagil R, Ball NJ, Ogrodowicz RW, Hobor F, Purkiss AG, Kelly G, Martin SR, Taylor IA, Ramos A Nucleic Acids Res. 2019 Mar 13. pii: 5377473. doi: 10.1093/nar/gkz136. PMID:30864660^[16]

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

References

↑ Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol Cell Biol. 1999 Feb;19(2):1262-70. PMID:9891060
↑ Patel GP, Ma S, Bag J. The autoregulatory translational control element of poly(A)-binding protein mRNA forms a heteromeric ribonucleoprotein complex. Nucleic Acids Res. 2005 Dec 14;33(22):7074-89. Print 2005. PMID:16356927 doi:33/22/7074
↑ Prokipcak RD, Herrick DJ, Ross J. Purification and properties of a protein that binds to the C-terminal coding region of human c-myc mRNA. J Biol Chem. 1994 Mar 25;269(12):9261-9. PMID:8132663
↑ Runge S, Nielsen FC, Nielsen J, Lykke-Andersen J, Wewer UM, Christiansen J. H19 RNA binds four molecules of insulin-like growth factor II mRNA-binding protein. J Biol Chem. 2000 Sep 22;275(38):29562-9. PMID:10875929 doi:10.1074/jbc.M001156200
↑ Lemm I, Ross J. Regulation of c-myc mRNA decay by translational pausing in a coding region instability determinant. Mol Cell Biol. 2002 Jun;22(12):3959-69. PMID:12024010
↑ Vikesaa J, Hansen TV, Jonson L, Borup R, Wewer UM, Christiansen J, Nielsen FC. RNA-binding IMPs promote cell adhesion and invadopodia formation. EMBO J. 2006 Apr 5;25(7):1456-68. Epub 2006 Mar 16. PMID:16541107 doi:7601039
↑ Stohr N, Lederer M, Reinke C, Meyer S, Hatzfeld M, Singer RH, Huttelmaier S. ZBP1 regulates mRNA stability during cellular stress. J Cell Biol. 2006 Nov 20;175(4):527-34. Epub 2006 Nov 13. PMID:17101699 doi:10.1083/jcb.200608071
↑ Noubissi FK, Elcheva I, Bhatia N, Shakoori A, Ougolkov A, Liu J, Minamoto T, Ross J, Fuchs SY, Spiegelman VS. CRD-BP mediates stabilization of betaTrCP1 and c-myc mRNA in response to beta-catenin signalling. Nature. 2006 Jun 15;441(7095):898-901. PMID:16778892 doi:nature04839
↑ Kato T, Hayama S, Yamabuki T, Ishikawa N, Miyamoto M, Ito T, Tsuchiya E, Kondo S, Nakamura Y, Daigo Y. Increased expression of insulin-like growth factor-II messenger RNA-binding protein 1 is associated with tumor progression in patients with lung cancer. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):434-42. PMID:17255263 doi:13/2/434
↑ Pan F, Huttelmaier S, Singer RH, Gu W. ZBP2 facilitates binding of ZBP1 to beta-actin mRNA during transcription. Mol Cell Biol. 2007 Dec;27(23):8340-51. Epub 2007 Sep 24. PMID:17893325 doi:10.1128/MCB.00972-07
↑ Zhou Y, Rong L, Lu J, Pan Q, Liang C. Insulin-like growth factor II mRNA binding protein 1 associates with Gag protein of human immunodeficiency virus type 1, and its overexpression affects virus assembly. J Virol. 2008 Jun;82(12):5683-92. doi: 10.1128/JVI.00189-08. Epub 2008 Apr 2. PMID:18385235 doi:10.1128/JVI.00189-08
↑ Elcheva I, Goswami S, Noubissi FK, Spiegelman VS. CRD-BP protects the coding region of betaTrCP1 mRNA from miR-183-mediated degradation. Mol Cell. 2009 Jul 31;35(2):240-6. doi: 10.1016/j.molcel.2009.06.007. PMID:19647520 doi:10.1016/j.molcel.2009.06.007
↑ Weidensdorfer D, Stohr N, Baude A, Lederer M, Kohn M, Schierhorn A, Buchmeier S, Wahle E, Huttelmaier S. Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs. RNA. 2009 Jan;15(1):104-15. doi: 10.1261/rna.1175909. Epub 2008 Nov 24. PMID:19029303 doi:10.1261/rna.1175909
↑ Weinlich S, Huttelmaier S, Schierhorn A, Behrens SE, Ostareck-Lederer A, Ostareck DH. IGF2BP1 enhances HCV IRES-mediated translation initiation via the 3'UTR. RNA. 2009 Aug;15(8):1528-42. doi: 10.1261/rna.1578409. Epub 2009 Jun 18. PMID:19541769 doi:10.1261/rna.1578409
↑ Chao JA, Patskovsky Y, Patel V, Levy M, Almo SC, Singer RH. ZBP1 recognition of beta-actin zipcode induces RNA looping. Genes Dev. 2010 Jan 15;24(2):148-58. PMID:20080952 doi:24/2/148
↑ Dagil R, Ball NJ, Ogrodowicz RW, Hobor F, Purkiss AG, Kelly G, Martin SR, Taylor IA, Ramos A. IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties. Nucleic Acids Res. 2019 Mar 13. pii: 5377473. doi: 10.1093/nar/gkz136. PMID:30864660 doi:http://dx.doi.org/10.1093/nar/gkz136

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6qey"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6qey is ON HOLD  until Paper Publication
+==IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties==
+<StructureSection load='6qey' size='340' side='right'caption='[[6qey]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6qey]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QEY FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CCN:ACETONITRILE'>CCN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qey OCA], [http://pdbe.org/6qey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qey RCSB], [http://www.ebi.ac.uk/pdbsum/6qey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qey ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/IF2B1_HUMAN IF2B1_HUMAN]] RNA-binding factor that affects mRNA nuclear export, localization, stability and translation. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. Regulates mRNA stability during the integrated cellular stress response (ISR) in stress granules (SGs). Stabilizes the BTRC/FBW1A mRNA from degradation by disrupting miRNA-dependent interaction with AGO2. Identified in a HCV IRES-mediated translation complex, that enhances translation at the Hepatitis C virus (HCV) RNA-replicon via the internal ribosome entry site (IRES), but does not affect 5'cap-dependent translation. Acts as a HIV-1 retrovirus restriction factor that reduces HIV-1 assembly by inhibiting viral RNA packaging, assembly and processing of HIV-1 GAG protein on cellular membranes. Binds to mRNAs in stress granules (SGs). Binds to the stem-loop IV of the 5'-UTR and to the variable region and the poly(U-C) motif of the 3'-UTR of the HCV RNA-replicon. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulates its subcellular localization and translation. Binds both to the coding region mRNA stability determinant (CRD) and to AU-rich sequences in the 3'-UTR of the MYC and CD44 mRNAs and stabilizes these mRNAs. Binds to the fourth and fifth exons of the oncofetal H19 and neuron-specific TAU mRNAs and regulates their localizations. Binds to the adenine-rich autoregulatory sequence (ARS) 5'-UTR of the PABPC1 mRNA and is involved in its translational repression. The RNA-binding activity to ARS is stimulated by PABPC1. Binds to the coding sequence region of BTRC/FBW1A mRNA and mediates stabilization of BTRC/FBW1A and MYC mRNAs in response to beta-catenin signaling. Binding to RNA employs a cooperative, sequential mechanism of homo- or heterodimerisation. Also involved in growth or survival of lung-cancer cells. Protects the MYC and MDR-1 mRNAs from cleavage by a endoribonuclease, thus prolonging their stabilities (By similarity). Binds to the 3'-UTR axonal localization signal (ALS) of TAU mRNA (By similarity). Binds to a conserved 54-nucleotide element in the 3'-UTR of the beta actin mRNA known as the 'zipcode' (By similarity). Promotes translocation of the beta-actin mRNA to dendrites (By similarity). May act as a regulator of mRNA transport to activated synapses in response to synaptic activity (By similarity).<ref>PMID:9891060</ref> <ref>PMID:16356927</ref> <ref>PMID:8132663</ref> <ref>PMID:10875929</ref> <ref>PMID:12024010</ref> <ref>PMID:16541107</ref> <ref>PMID:17101699</ref> <ref>PMID:16778892</ref> <ref>PMID:17255263</ref> <ref>PMID:17893325</ref> <ref>PMID:18385235</ref> <ref>PMID:19647520</ref> <ref>PMID:19029303</ref> <ref>PMID:19541769</ref> <ref>PMID:20080952</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit. Importantly, the high-affinity RNA-binding by KH1KH2 is achieved by an inter-domain coupling 50-fold stronger than that existing in a second pseudo-dimer in the protein, KH3KH4. The presence of this strong coupling supports a role of RNA re-modelling in IMP1 recognition of known cancer targets.
-Authors:
+IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.,Dagil R, Ball NJ, Ogrodowicz RW, Hobor F, Purkiss AG, Kelly G, Martin SR, Taylor IA, Ramos A Nucleic Acids Res. 2019 Mar 13. pii: 5377473. doi: 10.1093/nar/gkz136. PMID:30864660<ref>PMID:30864660</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6qey" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Ball, N J]]
+[[Category: Dagil, R]]
+[[Category: Ogrodowicz, R W]]
+[[Category: Purkiss, A G]]
+[[Category: Ramos, A]]
+[[Category: Taylor, I A]]
+[[Category: Imp1]]
+[[Category: Kh domain]]
+[[Category: Rna binding protein]]
+[[Category: Rna-binding]]

6qey

From Proteopedia

Revision as of 06:48, 27 March 2019

IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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