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| - | [[Image:1txp.gif|left|200px]] | |
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| - | {{Structure
| + | ==Heterogeneous Nuclear Ribonucleoprotein (hnRNP) C Oligomerization Domain Tetramer== |
| - | |PDB= 1txp |SIZE=350|CAPTION= <scene name='initialview01'>1txp</scene>
| + | <StructureSection load='1txp' size='340' side='right'caption='[[1txp]]' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[1txp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TXP FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | |GENE= HnRNP C1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1txp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1txp OCA], [https://pdbe.org/1txp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1txp RCSB], [https://www.ebi.ac.uk/pdbsum/1txp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1txp ProSAT]</span></td></tr> |
| - | |DOMAIN=
| + | </table> |
| - | |RELATEDENTRY= | + | == Function == |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1txp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1txp OCA], [http://www.ebi.ac.uk/pdbsum/1txp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1txp RCSB]</span>
| + | [https://www.uniprot.org/uniprot/HNRPC_HUMAN HNRPC_HUMAN] Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles. Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides. May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules.<ref>PMID:8264621</ref> <ref>PMID:7567451</ref> <ref>PMID:12509468</ref> <ref>PMID:16010978</ref> |
| - | }}
| + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | During active cell division, heterogeneous nuclear ribonucleoprotein (hnRNP) C is one of the most abundant proteins in the nucleus. hnRNP C exists as a stable tetramer that binds about 230 nucleotides of pre-mRNA and functions in vivo to package nascent transcripts and nucleate assembly of the 40 S hnRNP complex. Previous studies have shown that monomers lacking or possessing mutant oligomerization domains bind RNA with low affinity, strongly suggesting a cooperative protomer-RNA binding mode. In order to understand the role of the oligomerization domain in defining the biological functions and structure of hnRNP C tetramers, we have determined the high-resolution NMR structure of the oligomerization interface that is formed at the core of the complex, examining specific molecular interactions that drive assembly and contribute to the structural integrity of the tetramer. The determined structure reveals an antiparallel four-helix coiled coil, where classically described knobs-into-holes packing interactions at interhelical contact surfaces are optimized so that side-chains interdigitate to create an even distribution of hydrophobic surfaces along the core. While the stoichiometry of the complex appears to be primarily specified by occlusion of hydrophobic surfaces, particularly the interfacial residue L198, from solvent, helix orientation is primarily determined by electrostatic attractions across helix interfaces. The creation of potential interaction surfaces for other hnRNP C domains along the coiled coil exterior and the assembly of oligomerization interfaces in an antiparallel orientation shape the tertiary fold of full-length monomers and juxtapose RNA-binding elements at distal surfaces of the tetrameric complex in the quaternary assembly. In addition, we discuss the specific challenges encountered in structure determination of this symmetric oligomer by NMR methods, specifically in sorting ambiguous interatomic distance constraints into classes that define different elements of the coiled coil structure. |
| | | | |
| - | '''Heterogeneous Nuclear Ribonucleoprotein (hnRNP) C Oligomerization Domain Tetramer'''
| + | Solution structure of the symmetric coiled coil tetramer formed by the oligomerization domain of hnRNP C: implications for biological function.,Whitson SR, LeStourgeon WM, Krezel AM J Mol Biol. 2005 Jul 8;350(2):319-37. PMID:15936032<ref>PMID:15936032</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 1txp" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | During active cell division, heterogeneous nuclear ribonucleoprotein (hnRNP) C is one of the most abundant proteins in the nucleus. hnRNP C exists as a stable tetramer that binds about 230 nucleotides of pre-mRNA and functions in vivo to package nascent transcripts and nucleate assembly of the 40 S hnRNP complex. Previous studies have shown that monomers lacking or possessing mutant oligomerization domains bind RNA with low affinity, strongly suggesting a cooperative protomer-RNA binding mode. In order to understand the role of the oligomerization domain in defining the biological functions and structure of hnRNP C tetramers, we have determined the high-resolution NMR structure of the oligomerization interface that is formed at the core of the complex, examining specific molecular interactions that drive assembly and contribute to the structural integrity of the tetramer. The determined structure reveals an antiparallel four-helix coiled coil, where classically described knobs-into-holes packing interactions at interhelical contact surfaces are optimized so that side-chains interdigitate to create an even distribution of hydrophobic surfaces along the core. While the stoichiometry of the complex appears to be primarily specified by occlusion of hydrophobic surfaces, particularly the interfacial residue L198, from solvent, helix orientation is primarily determined by electrostatic attractions across helix interfaces. The creation of potential interaction surfaces for other hnRNP C domains along the coiled coil exterior and the assembly of oligomerization interfaces in an antiparallel orientation shape the tertiary fold of full-length monomers and juxtapose RNA-binding elements at distal surfaces of the tetrameric complex in the quaternary assembly. In addition, we discuss the specific challenges encountered in structure determination of this symmetric oligomer by NMR methods, specifically in sorting ambiguous interatomic distance constraints into classes that define different elements of the coiled coil structure.
| + | *[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 1TXP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TXP OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | Solution structure of the symmetric coiled coil tetramer formed by the oligomerization domain of hnRNP C: implications for biological function., Whitson SR, LeStourgeon WM, Krezel AM, J Mol Biol. 2005 Jul 8;350(2):319-37. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15936032 15936032]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Krezel, A M.]] | + | [[Category: Krezel AM]] |
| - | [[Category: Lestourgeon, W M.]] | + | [[Category: Lestourgeon WM]] |
| - | [[Category: Whitson, S R.]] | + | [[Category: Whitson SR]] |
| - | [[Category: antiparallel four helix coiled coil tetramer hnrnpc]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:02:32 2008''
| + | |
| Structural highlights
Function
HNRPC_HUMAN Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles. Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides. May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules.[1] [2] [3] [4]
Publication Abstract from PubMed
During active cell division, heterogeneous nuclear ribonucleoprotein (hnRNP) C is one of the most abundant proteins in the nucleus. hnRNP C exists as a stable tetramer that binds about 230 nucleotides of pre-mRNA and functions in vivo to package nascent transcripts and nucleate assembly of the 40 S hnRNP complex. Previous studies have shown that monomers lacking or possessing mutant oligomerization domains bind RNA with low affinity, strongly suggesting a cooperative protomer-RNA binding mode. In order to understand the role of the oligomerization domain in defining the biological functions and structure of hnRNP C tetramers, we have determined the high-resolution NMR structure of the oligomerization interface that is formed at the core of the complex, examining specific molecular interactions that drive assembly and contribute to the structural integrity of the tetramer. The determined structure reveals an antiparallel four-helix coiled coil, where classically described knobs-into-holes packing interactions at interhelical contact surfaces are optimized so that side-chains interdigitate to create an even distribution of hydrophobic surfaces along the core. While the stoichiometry of the complex appears to be primarily specified by occlusion of hydrophobic surfaces, particularly the interfacial residue L198, from solvent, helix orientation is primarily determined by electrostatic attractions across helix interfaces. The creation of potential interaction surfaces for other hnRNP C domains along the coiled coil exterior and the assembly of oligomerization interfaces in an antiparallel orientation shape the tertiary fold of full-length monomers and juxtapose RNA-binding elements at distal surfaces of the tetrameric complex in the quaternary assembly. In addition, we discuss the specific challenges encountered in structure determination of this symmetric oligomer by NMR methods, specifically in sorting ambiguous interatomic distance constraints into classes that define different elements of the coiled coil structure.
Solution structure of the symmetric coiled coil tetramer formed by the oligomerization domain of hnRNP C: implications for biological function.,Whitson SR, LeStourgeon WM, Krezel AM J Mol Biol. 2005 Jul 8;350(2):319-37. PMID:15936032[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang M, Rech JE, Northington SJ, Flicker PF, Mayeda A, Krainer AR, LeStourgeon WM. The C-protein tetramer binds 230 to 240 nucleotides of pre-mRNA and nucleates the assembly of 40S heterogeneous nuclear ribonucleoprotein particles. Mol Cell Biol. 1994 Jan;14(1):518-33. PMID:8264621
- ↑ Sebillon P, Beldjord C, Kaplan JC, Brody E, Marie J. A T to G mutation in the polypyrimidine tract of the second intron of the human beta-globin gene reduces in vitro splicing efficiency: evidence for an increased hnRNP C interaction. Nucleic Acids Res. 1995 Sep 11;23(17):3419-25. PMID:7567451
- ↑ Kim JH, Paek KY, Choi K, Kim TD, Hahm B, Kim KT, Jang SK. Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in a cell cycle phase-dependent manner. Mol Cell Biol. 2003 Jan;23(2):708-20. PMID:12509468
- ↑ Shetty S. Regulation of urokinase receptor mRNA stability by hnRNP C in lung epithelial cells. Mol Cell Biochem. 2005 Apr;272(1-2):107-18. PMID:16010978
- ↑ Whitson SR, LeStourgeon WM, Krezel AM. Solution structure of the symmetric coiled coil tetramer formed by the oligomerization domain of hnRNP C: implications for biological function. J Mol Biol. 2005 Jul 8;350(2):319-37. PMID:15936032 doi:S0022-2836(05)00522-X
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