5zf6
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Crystal structure of the dimeric human PNPase== |
| + | <StructureSection load='5zf6' size='340' side='right' caption='[[5zf6]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5zf6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZF6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZF6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polyribonucleotide_nucleotidyltransferase Polyribonucleotide nucleotidyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.8 2.7.7.8] </span></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=5zf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zf6 OCA], [http://pdbe.org/5zf6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zf6 RCSB], [http://www.ebi.ac.uk/pdbsum/5zf6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zf6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/PNPT1_HUMAN PNPT1_HUMAN]] Combined oxidative phosphorylation defect type 13;Autosomal recessive nonsyndromic sensorineural deafness type DFNB. Combined oxidative phosphorylation deficiency 13 (COXPD13) [MIM:[http://omim.org/entry/614932 614932]]: A mitochondrial disorder characterized by early onset severe encephalomyopathy, dystonia, choreoathetosis, bucofacial dyskinesias and combined mitochondrial respiratory chain deficiency. Nerve conductions velocities are decreased. Levels of plasma and cerebrospinal fluid lactate are increased. Note=The disease is caused by mutations affecting the gene represented in this entry. Deafness, autosomal recessive, 70 (DFNB70) [MIM:[http://omim.org/entry/614934 614934]]: A form of non-syndromic deafness characterized by severe, bilateral hearing impairment with prelingual onset, resulting in inability to acquire normal speech. Note=The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PNPT1_HUMAN PNPT1_HUMAN]] RNA-binding protein implicated in numerous RNA metabolic processes. Hydrolyzes single-stranded polyribonucleotides processively in the 3'-to-5' direction. Mitochondrial intermembrane factor with RNA-processing exoribonulease activity. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Required for correct processing and polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic RNA import factor that mediates the translocation of small RNA components, like the 5S RNA, the RNA subunit of ribonuclease P and the mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. Plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' exoribonuclease mediating mRNA degradation activity; degrades c-myc mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest in melanoma cells. Regulates the stability of specific mature miRNAs in melanoma cells; specifically and selectively degrades miR-221, preferentially. Plays also a role in RNA cell surveillance by cleaning up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA and miR-221 microRNA.<ref>PMID:12473748</ref> <ref>PMID:12721301</ref> <ref>PMID:12798676</ref> <ref>PMID:16055741</ref> <ref>PMID:16410805</ref> <ref>PMID:16934922</ref> <ref>PMID:18501193</ref> <ref>PMID:18083836</ref> <ref>PMID:18083837</ref> <ref>PMID:19509288</ref> <ref>PMID:20691904</ref> <ref>PMID:20547861</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human polynucleotide phosphorylase (PNPase) is an evolutionarily conserved 3'-to-5' exoribonuclease principally located in mitochondria where it is responsible for RNA turnover and import. Mutations in PNPase impair structured RNA transport into mitochondria, resulting in mitochondrial dysfunction and disease. PNPase is a trimeric protein with a doughnut-shaped structure hosting a central channel for single-stranded RNA binding and degradation. Here, we show that the disease-linked human PNPase mutants, Q387R and E475G, form dimers, not trimers, and have significantly lower RNA binding and degradation activities compared to wild-type trimeric PNPase. Moreover, S1 domain-truncated PNPase binds single-stranded RNA but not the stem-loop signature motif of imported structured RNA, suggesting that the S1 domain is responsible for binding structured RNAs. We further determined the crystal structure of dimeric PNPase at a resolution of 2.8 A and, combined with small-angle X-ray scattering, show that the RNA-binding K homology and S1 domains are relatively inaccessible in the dimeric assembly. Taken together, these results show that mutations at the interface of the trimeric PNPase tend to produce a dimeric protein with destructive RNA-binding surfaces, thus impairing both of its RNA import and degradation activities and leading to mitochondria disorders. | ||
| - | + | Crystal structure of dimeric human PNPase reveals why disease-linked mutants suffer from low RNA import and degradation activities.,Golzarroshan B, Lin CL, Li CL, Yang WZ, Chu LY, Agrawal S, Yuan HS Nucleic Acids Res. 2018 Jul 18. pii: 5055393. doi: 10.1093/nar/gky642. PMID:30020492<ref>PMID:30020492</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5zf6" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Polyribonucleotide nucleotidyltransferase]] | ||
[[Category: Golzarroshan, B]] | [[Category: Golzarroshan, B]] | ||
| + | [[Category: Yuan, H S]] | ||
| + | [[Category: Dimeric human pnpase]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 06:01, 22 August 2018
Crystal structure of the dimeric human PNPase
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