2n8m

From Proteopedia

(Difference between revisions)

Revision as of 07:46, 12 December 2018

Zipcode-binding-protein-1 KH3(DD)KH4 domains in complex with the KH4 RNA target

Structural highlights

2n8m is a 2 chain structure with sequence from Chick. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2n8l
Gene:	IGF2BP1, VICKZ1, ZBP1 (CHICK)
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]

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^[8]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

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/2n8m"

@@ Line 3: / Line 3: @@
 <StructureSection load='2n8m' size='340' side='right' caption='[[2n8m]], [[NMR_Ensembles_of_Models | 12 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2n8m]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N8M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2n8m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N8M FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n8l|2n8l]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGF2BP1, VICKZ1, ZBP1 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2n8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n8m OCA], [http://pdbe.org/2n8m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n8m RCSB], [http://www.ebi.ac.uk/pdbsum/2n8m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n8m ProSAT]</span></td></tr>
 </table>
@@ Line 11: / Line 12: @@
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-In eukaryotes, RNA-binding proteins that contain multiple K homology (KH) domains play a key role in coordinating the different steps of RNA synthesis, metabolism and localization. Understanding how the different KH modules participate in the recognition of the RNA targets is necessary to dissect the way these proteins operate. We have designed a KH mutant with impaired RNA-binding capability for general use in exploring the role of individual KH domains in the combinatorial functional recognition of RNA targets. A double mutation in the hallmark GxxG loop (GxxG-to-GDDG) impairs nucleic acid binding without compromising the stability of the domain. We analysed the impact of the GDDG mutations in individual KH domains on the functional properties of KSRP as a prototype of multiple KH domain-containing proteins. We show how the GDDG mutant can be used to directly link biophysical information on the sequence specificity of the different KH domains of KSRP and their role in mRNA recognition and decay. This work defines a general molecular biology tool for the investigation of the function of individual KH domains in nucleic acid binding proteins.
+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.
-KH domains with impaired nucleic acid binding as a tool for functional analysis.,Hollingworth D, Candel AM, Nicastro G, Martin SR, Briata P, Gherzi R, Ramos A Nucleic Acids Res. 2012 Aug;40(14):6873-86. doi: 10.1093/nar/gks368. Epub 2012, Apr 29. PMID:22547390<ref>PMID:22547390</ref>
+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>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Chick]]
 [[Category: Candel, A]]
 [[Category: Hollingworth, D]]

2n8m

From Proteopedia

Revision as of 07:46, 12 December 2018

Zipcode-binding-protein-1 KH3(DD)KH4 domains in complex with the KH4 RNA target

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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