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| | ==Solution structure of the P22S mutant of N-terminal CS domain of human Shq1== | | ==Solution structure of the P22S mutant of N-terminal CS domain of human Shq1== |
| - | <StructureSection load='2mnw' size='340' side='right' caption='[[2mnw]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mnw' size='340' side='right'caption='[[2mnw]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mnw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MNW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MNW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mnw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MNW FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pbd|4pbd]], [[4pck|4pck]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4pbd|4pbd]], [[4pck|4pck]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SHQ1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SHQ1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2mnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mnw OCA], [http://pdbe.org/2mnw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mnw RCSB], [http://www.ebi.ac.uk/pdbsum/2mnw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mnw ProSAT]</span></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=2mnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mnw OCA], [https://pdbe.org/2mnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mnw RCSB], [https://www.ebi.ac.uk/pdbsum/2mnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mnw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SHQ1_HUMAN SHQ1_HUMAN]] Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs), including telomerase, probably through the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA.<ref>PMID:19383767</ref> | + | [[https://www.uniprot.org/uniprot/SHQ1_HUMAN SHQ1_HUMAN]] Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs), including telomerase, probably through the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA.<ref>PMID:19383767</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Cascio, D]] | | [[Category: Cascio, D]] |
| | [[Category: Feigon, J]] | | [[Category: Feigon, J]] |
| Structural highlights
Function
[SHQ1_HUMAN] Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs), including telomerase, probably through the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA.[1]
Publication Abstract from PubMed
Shq1 is an essential protein involved in the early steps of biogenesis and assembly of H/ACA RNPs. Shq1 binds to dyskerin (Cbf5 in yeast) at an early step of H/ACA RNP assembly and is subsequently displaced by the H/ACA RNA. Shq1 contains an N-terminal CS and a C-terminal Shq1-specific domain (SSD). Dyskerin harbors many dyskeratosis congenita (DC) associated mutations. Structures of yeast Shq1 SSD bound to Cbf5 revealed that only a subset of these mutations is in the SSD binding site, implicating another subset in the putative CS binding site. Here we present the crystal structure of human Shq1 CS (hCS) and the NMR and crystal structure of hCS containing a serine substitution for proline 22 that is associated with some prostate cancers. The structure of hCS is similar to yeast Shq1 CS domain (yCS) and consists of two beta-sheets that form an immunoglobulin-like beta-sandwich fold. The N-terminal affinity tag sequence AHHHHHH associates with a neighboring protein in the crystal lattice to form an extra beta-strand. Deletion of this tag was required to get spectra suitable for NMR structure determination, while the tag was required for crystallization. NMR chemical shift perturbation (CSP) experiments with dyskerin and Cbf5 derived peptides from putative CS binding sites revealed a conserved surface on CS important for Cbf5/dyskerin binding. A HADDOCK docking model of a Shq1-Cbf5 complex that defines the position of CS domain in the pre-H/ACA RNP was calculated using the CSP data.
Structure and interactions of the CS domain of human H/ACA RNP assembly protein Shq1.,Singh M, Wang Z, Cascio D, Feigon J J Mol Biol. 2014 Dec 29. pii: S0022-2836(14)00646-9. doi:, 10.1016/j.jmb.2014.12.012. PMID:25553844[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grozdanov PN, Roy S, Kittur N, Meier UT. SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and telomerase RNPs. RNA. 2009 Jun;15(6):1188-97. Epub 2009 Apr 21. PMID:19383767 doi:http://dx.doi.org/rna.1532109
- ↑ Singh M, Wang Z, Cascio D, Feigon J. Structure and interactions of the CS domain of human H/ACA RNP assembly protein Shq1. J Mol Biol. 2014 Dec 29. pii: S0022-2836(14)00646-9. doi:, 10.1016/j.jmb.2014.12.012. PMID:25553844 doi:http://dx.doi.org/10.1016/j.jmb.2014.12.012
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