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==Zipcode-binding-protein-1 KH3KH4(DD) domains in complex with the KH3 RNA target==
==Zipcode-binding-protein-1 KH3KH4(DD) domains in complex with the KH3 RNA target==
<StructureSection load='2n8l' size='340' side='right'caption='[[2n8l]], [[NMR_Ensembles_of_Models | 12 NMR models]]' scene=''>
<StructureSection load='2n8l' size='340' side='right'caption='[[2n8l]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2n8l]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chick Chick]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N8L FirstGlance]. <br>
<table><tr><td colspan='2'>[[2n8l]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N8L FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2n8m|2n8m]]</div></td></tr>
</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=2n8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n8l OCA], [https://pdbe.org/2n8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n8l RCSB], [https://www.ebi.ac.uk/pdbsum/2n8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n8l ProSAT]</span></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGF2BP1, VICKZ1, ZBP1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</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=2n8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n8l OCA], [https://pdbe.org/2n8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n8l RCSB], [https://www.ebi.ac.uk/pdbsum/2n8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n8l ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/IF2B1_CHICK IF2B1_CHICK]] RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons (By similarity). Regulates localized beta-actin/ACTB mRNA translation in polarized cells, a crucial process for cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves by a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The ribonucleoparticle (RNP) thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, IGF2BP1 prevents beta-actin mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated by SRC. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. The monomeric ACTB protein then assembles into the subcortical actin cytoskeleton, which pushes the leading edge onwards. Binds MYC mRNA. Promotes the directed movement of cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization.<ref>PMID:11502257</ref> <ref>PMID:12507992</ref> <ref>PMID:12573215</ref> <ref>PMID:16306994</ref> <ref>PMID:22279049</ref> <ref>PMID:23640942</ref> <ref>PMID:9121465</ref> 
[https://www.uniprot.org/uniprot/IF2B1_CHICK IF2B1_CHICK] RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons (By similarity). Regulates localized beta-actin/ACTB mRNA translation in polarized cells, a crucial process for cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves by a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The ribonucleoparticle (RNP) thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, IGF2BP1 prevents beta-actin mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated by SRC. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. The monomeric ACTB protein then assembles into the subcortical actin cytoskeleton, which pushes the leading edge onwards. Binds MYC mRNA. Promotes the directed movement of cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization.<ref>PMID:11502257</ref> <ref>PMID:12507992</ref> <ref>PMID:12573215</ref> <ref>PMID:16306994</ref> <ref>PMID:22279049</ref> <ref>PMID:23640942</ref> <ref>PMID:9121465</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ZBP1 (zipcode-binding protein 1) was originally discovered as a trans-acting factor for the "zipcode" in the 3' untranslated region (UTR) of the beta-actin mRNA that is important for its localization and translational regulation. Subsequently, ZBP1 has been found to be a multifunctional regulator of RNA metabolism that controls aspects of localization, stability, and translation for many mRNAs. To reveal how ZBP1 recognizes its RNA targets, we biochemically characterized the interaction between ZBP1 and the beta-actin zipcode. The third and fourth KH (hnRNP K homology) domains of ZBP1 specifically recognize a bipartite RNA element located within the first 28 nucleotides of the zipcode. The spacing between the RNA sequences is consistent with the structure of IMP1 KH34, the human ortholog of ZBP1, that we solved by X-ray crystallography. The tandem KH domains are arranged in an intramolecular anti-parallel pseudodimer conformation with the canonical RNA-binding surfaces at opposite ends of the molecule. This orientation of the KH domains requires that the RNA backbone must undergo an approximately 180 degrees change in direction in order for both KH domains to contact the RNA simultaneously. The RNA looping induced by ZBP1 binding provides a mechanism for specific recognition and may facilitate the assembly of post-transcriptional regulatory complexes by remodeling the bound transcript.
 
ZBP1 recognition of beta-actin zipcode induces RNA looping.,Chao JA, Patskovsky Y, Patel V, Levy M, Almo SC, Singer RH Genes Dev. 2010 Jan 15;24(2):148-58. PMID:20080952<ref>PMID:20080952</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2n8l" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Chick]]
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Candel, A M]]
[[Category: Synthetic construct]]
[[Category: Hollingworth, D]]
[[Category: Candel AM]]
[[Category: Nicastro, G]]
[[Category: Hollingworth D]]
[[Category: Ramos, A]]
[[Category: Nicastro G]]
[[Category: Kh domain]]
[[Category: Ramos A]]
[[Category: Rna binding protein-rna complex]]

Latest revision as of 13:23, 15 March 2023

Zipcode-binding-protein-1 KH3KH4(DD) domains in complex with the KH3 RNA targetZipcode-binding-protein-1 KH3KH4(DD) domains in complex with the KH3 RNA target

Structural highlights

2n8l is a 2 chain structure with sequence from Gallus gallus and Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IF2B1_CHICK RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons (By similarity). Regulates localized beta-actin/ACTB mRNA translation in polarized cells, a crucial process for cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves by a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The ribonucleoparticle (RNP) thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, IGF2BP1 prevents beta-actin mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated by SRC. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. The monomeric ACTB protein then assembles into the subcortical actin cytoskeleton, which pushes the leading edge onwards. Binds MYC mRNA. Promotes the directed movement of cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization.[1] [2] [3] [4] [5] [6] [7]

See Also

References

  1. ↑ Zhang HL, Eom T, Oleynikov Y, Shenoy SM, Liebelt DA, Dictenberg JB, Singer RH, Bassell GJ. Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility. Neuron. 2001 Aug 2;31(2):261-75. PMID:11502257
  2. ↑ Farina KL, Huttelmaier S, Musunuru K, Darnell R, Singer RH. Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment. J Cell Biol. 2003 Jan 6;160(1):77-87. Epub 2002 Dec 30. PMID:12507992 doi:http://dx.doi.org/10.1083/jcb.200206003
  3. ↑ Oleynikov Y, Singer RH. Real-time visualization of ZBP1 association with beta-actin mRNA during transcription and localization. Curr Biol. 2003 Feb 4;13(3):199-207. PMID:12573215
  4. ↑ Huttelmaier S, Zenklusen D, Lederer M, Dictenberg J, Lorenz M, Meng X, Bassell GJ, Condeelis J, Singer RH. Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1. Nature. 2005 Nov 24;438(7067):512-5. PMID:16306994 doi:nature04115
  5. ↑ Stohr N, Kohn M, Lederer M, Glass M, Reinke C, Singer RH, Huttelmaier S. IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. Genes Dev. 2012 Jan 15;26(2):176-89. doi: 10.1101/gad.177642.111. PMID:22279049 doi:http://dx.doi.org/10.1101/gad.177642.111
  6. ↑ Wachter K, Kohn M, Stohr N, Huttelmaier S. Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains. Biol Chem. 2013 Aug;394(8):1077-90. doi: 10.1515/hsz-2013-0111. PMID:23640942 doi:http://dx.doi.org/10.1515/hsz-2013-0111
  7. ↑ Ross AF, Oleynikov Y, Kislauskis EH, Taneja KL, Singer RH. Characterization of a beta-actin mRNA zipcode-binding protein. Mol Cell Biol. 1997 Apr;17(4):2158-65. PMID:9121465
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