5zf6

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the dimeric human PNPase

Structural highlights

5zf6 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.796Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PNPT1_HUMAN Combined oxidative phosphorylation defect type 13;Autosomal recessive nonsyndromic sensorineural deafness type DFNB. Combined oxidative phosphorylation deficiency 13 (COXPD13) [MIM: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: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

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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

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^[13]

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

References

↑ Leszczyniecka M, Kang DC, Sarkar D, Su ZZ, Holmes M, Valerie K, Fisher PB. Identification and cloning of human polynucleotide phosphorylase, hPNPase old-35, in the context of terminal differentiation and cellular senescence. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16636-41. Epub 2002 Dec 9. PMID:12473748 doi:10.1073/pnas.252643699
↑ Sarkar D, Leszczyniecka M, Kang DC, Lebedeva IV, Valerie K, Dhar S, Pandita TK, Fisher PB. Down-regulation of Myc as a potential target for growth arrest induced by human polynucleotide phosphorylase (hPNPaseold-35) in human melanoma cells. J Biol Chem. 2003 Jul 4;278(27):24542-51. Epub 2003 Apr 29. PMID:12721301 doi:10.1074/jbc.M302421200
↑ Piwowarski J, Grzechnik P, Dziembowski A, Dmochowska A, Minczuk M, Stepien PP. Human polynucleotide phosphorylase, hPNPase, is localized in mitochondria. J Mol Biol. 2003 Jun 20;329(5):853-7. PMID:12798676
↑ Sarkar D, Park ES, Emdad L, Randolph A, Valerie K, Fisher PB. Defining the domains of human polynucleotide phosphorylase (hPNPaseOLD-35) mediating cellular senescence. Mol Cell Biol. 2005 Aug;25(16):7333-43. PMID:16055741 doi:10.1128/MCB.25.16.7333-7343.2005
↑ Sarkar D, Park ES, Fisher PB. Defining the mechanism by which IFN-beta dowregulates c-myc expression in human melanoma cells: pivotal role for human polynucleotide phosphorylase (hPNPaseold-35). Cell Death Differ. 2006 Sep;13(9):1541-53. Epub 2006 Jan 13. PMID:16410805 doi:10.1038/sj.cdd.4401829
↑ French SW, Dawson DW, Chen HW, Rainey RN, Sievers SA, Balatoni CE, Wong L, Troke JJ, Nguyen MT, Koehler CM, Teitell MA. The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity. Cancer Lett. 2007 Apr 18;248(2):198-210. Epub 2006 Aug 28. PMID:16934922 doi:10.1016/j.canlet.2006.07.006
↑ Wu J, Li Z. Human polynucleotide phosphorylase reduces oxidative RNA damage and protects HeLa cell against oxidative stress. Biochem Biophys Res Commun. 2008 Jul 25;372(2):288-92. doi:, 10.1016/j.bbrc.2008.05.058. Epub 2008 May 21. PMID:18501193 doi:10.1016/j.bbrc.2008.05.058
↑ Portnoy V, Palnizky G, Yehudai-Resheff S, Glaser F, Schuster G. Analysis of the human polynucleotide phosphorylase (PNPase) reveals differences in RNA binding and response to phosphate compared to its bacterial and chloroplast counterparts. RNA. 2008 Feb;14(2):297-309. Epub 2007 Dec 14. PMID:18083836 doi:10.1261/rna.698108
↑ Slomovic S, Schuster G. Stable PNPase RNAi silencing: its effect on the processing and adenylation of human mitochondrial RNA. RNA. 2008 Feb;14(2):310-23. Epub 2007 Dec 14. PMID:18083837 doi:10.1261/rna.697308
↑ Wang DD, Shu Z, Lieser SA, Chen PL, Lee WH. Human mitochondrial SUV3 and polynucleotide phosphorylase form a 330-kDa heteropentamer to cooperatively degrade double-stranded RNA with a 3'-to-5' directionality. J Biol Chem. 2009 Jul 31;284(31):20812-21. Epub 2009 Jun 9. PMID:19509288 doi:M109.009605
↑ Wang G, Chen HW, Oktay Y, Zhang J, Allen EL, Smith GM, Fan KC, Hong JS, French SW, McCaffery JM, Lightowlers RN, Morse HC 3rd, Koehler CM, Teitell MA. PNPASE regulates RNA import into mitochondria. Cell. 2010 Aug 6;142(3):456-67. doi: 10.1016/j.cell.2010.06.035. PMID:20691904 doi:10.1016/j.cell.2010.06.035
↑ Das SK, Sokhi UK, Bhutia SK, Azab B, Su ZZ, Sarkar D, Fisher PB. Human polynucleotide phosphorylase selectively and preferentially degrades microRNA-221 in human melanoma cells. Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11948-53. doi:, 10.1073/pnas.0914143107. Epub 2010 Jun 14. PMID:20547861 doi:10.1073/pnas.0914143107
↑ Golzarroshan B, Lin CL, Li CL, Yang WZ, Chu LY, Agrawal S, Yuan HS. Crystal structure of dimeric human PNPase reveals why disease-linked mutants suffer from low RNA import and degradation activities. Nucleic Acids Res. 2018 Jul 18. pii: 5055393. doi: 10.1093/nar/gky642. PMID:30020492 doi:http://dx.doi.org/10.1093/nar/gky642

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5zf6"

Categories: Homo sapiens | Large Structures | Golzarroshan B | Yuan HS

@@ Line 1: / Line 1: @@
 ==Crystal structure of the dimeric human PNPase==
-<StructureSection load='5zf6' size='340' side='right' caption='[[5zf6]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='5zf6' size='340' side='right'caption='[[5zf6]], [[Resolution|resolution]] 2.80&Aring;' 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>
+<table><tr><td colspan='2'>[[5zf6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.796&#8491;</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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zf6 OCA], [https://pdbe.org/5zf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zf6 RCSB], [https://www.ebi.ac.uk/pdbsum/5zf6 PDBsum], [https://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.
+[https://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:[https://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:[https://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>
+[https://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 ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5zf6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Polyribonucleotide nucleotidyltransferase]]
+[[Category: Homo sapiens]]
-[[Category: Golzarroshan, B]]
+[[Category: Large Structures]]
-[[Category: Yuan, H S]]
+[[Category: Golzarroshan B]]
-[[Category: Dimeric human pnpase]]
+[[Category: Yuan HS]]
-[[Category: Transferase]]

5zf6

From Proteopedia

Current revision

Crystal structure of the dimeric human PNPase

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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