3u1k

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human PNPase

Structural highlights

3u1k is a 4 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 2.13Å
Ligands:
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 (hPNPase) is a 3'-to-5' exoribonuclease that degrades specific mRNA and miRNA, and imports RNA into mitochondria, and thus regulates diverse physiological processes, including cellular senescence and homeostasis. However, the RNA-processing mechanism by hPNPase, particularly how RNA is bound via its various domains, remains obscure. Here, we report the crystal structure of an S1 domain-truncated hPNPase at a resolution of 2.1 A. The trimeric hPNPase has a hexameric ring-like structure formed by six RNase PH domains, capped with a trimeric KH pore. Our biochemical and mutagenesis studies suggest that the S1 domain is not critical for RNA binding, and conversely, that the conserved GXXG motif in the KH domain directly participates in RNA binding in hPNPase. Our studies thus provide structural and functional insights into hPNPase, which uses a KH pore to trap a long RNA 3' tail that is further delivered into an RNase PH channel for the degradation process. Structural RNA with short 3' tails are, on the other hand, transported but not digested by hPNPase.

Crystal structure of human polynucleotide phosphorylase: insights into its domain function in RNA binding and degradation.,Lin CL, Wang YT, Yang WZ, Hsiao YY, Yuan HS Nucleic Acids Res. 2011 Dec 30. PMID:22210891^[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
↑ Lin CL, Wang YT, Yang WZ, Hsiao YY, Yuan HS. Crystal structure of human polynucleotide phosphorylase: insights into its domain function in RNA binding and degradation. Nucleic Acids Res. 2011 Dec 30. PMID:22210891 doi:10.1093/nar/gkr1281

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/3u1k"

Categories: Homo sapiens | Large Structures | Lin CL | Yuan HS

@@ Line 3: / Line 3: @@
 <StructureSection load='3u1k' size='340' side='right'caption='[[3u1k]], [[Resolution|resolution]] 2.13&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3u1k]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U1K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U1K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3u1k]] is a 4 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=3U1K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U1K FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></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]] 2.13&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PNPT1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Polyribonucleotide_nucleotidyltransferase Polyribonucleotide nucleotidyltransferase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3u1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u1k OCA], [https://pdbe.org/3u1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u1k RCSB], [https://www.ebi.ac.uk/pdbsum/3u1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u1k ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[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.
+[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 ==
-[[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>
+[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 22: / Line 21: @@
 </div>
 <div class="pdbe-citations 3u1k" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Polyribonucleotide nucleotidyltransferase]]
+[[Category: Lin CL]]
-[[Category: Lin, C L]]
+[[Category: Yuan HS]]
-[[Category: Yuan, H S]]
-[[Category: Exoribonuclease]]
-[[Category: Kh domain]]
-[[Category: Rnase ph]]
-[[Category: Transferase]]

3u1k

From Proteopedia

Current revision

Crystal structure of 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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