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3uvu

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Revision as of 07:51, 5 August 2016

Structural basis of nuclear import of Flap endonuclease 1 (FEN1)

Structural highlights

3uvu is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1pjn, 3rzx, 1pjm, 3rz9
Gene:	Kpna2, Rch1 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FEN1_HUMAN] Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] [IMA2_MOUSE] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.

Publication Abstract from PubMed

Flap endonuclease 1 (FEN1) is a member of the nuclease family and is structurally conserved from bacteriophages to humans. This protein is involved in multiple DNA-processing pathways, including Okazaki fragment maturation, stalled replication-fork rescue, telomere maintenance, long-patch base-excision repair and apoptotic DNA fragmentation. FEN1 has three functional motifs that are responsible for its nuclease, PCNA-interaction and nuclear localization activities, respectively. It has been shown that the C-terminal nuclear localization sequence (NLS) facilitates nuclear localization of the enzyme during the S phase of the cell cycle and in response to DNA damage. To determine the structural basis of the recognition of FEN1 by the nuclear import receptor importin alpha, the crystal structure of the complex of importin alpha with a peptide corresponding to the FEN1 NLS was solved. Structural studies confirmed the binding of the FEN1 NLS as a classical bipartite NLS; however, in contrast to the previously proposed (354)KRKX(8)KKK(367) sequence, it is the (354)KRX(10)KKAK(369) sequence that binds to importin alpha. This result explains the incomplete inhibition of localization that was observed on mutating residues (365)KKK(367). Acidic and polar residues in the X(10) linker region close to the basic clusters play an important role in binding to importin alpha. These results suggest that the basic residues in the N-terminal basic cluster of bipartite NLSs may play roles that are more critical than those of the many basic residues in the C-terminal basic cluster.

Structural basis of nuclear import of flap endonuclease 1 (FEN1).,de Barros AC, Takeda AA, Chang CW, Kobe B, Fontes MR Acta Crystallogr D Biol Crystallogr. 2012 Jul;68(Pt 7):743-50. doi:, 10.1107/S0907444912010281. Epub 2012 Jun 15. PMID:22751659^[7]

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

References

↑ Robins P, Pappin DJ, Wood RD, Lindahl T. Structural and functional homology between mammalian DNase IV and the 5'-nuclease domain of Escherichia coli DNA polymerase I. J Biol Chem. 1994 Nov 18;269(46):28535-8. PMID:7961795
↑ Shen B, Nolan JP, Sklar LA, Park MS. Essential amino acids for substrate binding and catalysis of human flap endonuclease 1. J Biol Chem. 1996 Apr 19;271(16):9173-6. PMID:8621570
↑ Tom S, Henricksen LA, Bambara RA. Mechanism whereby proliferating cell nuclear antigen stimulates flap endonuclease 1. J Biol Chem. 2000 Apr 7;275(14):10498-505. PMID:10744741
↑ Qiu J, Bimston DN, Partikian A, Shen B. Arginine residues 47 and 70 of human flap endonuclease-1 are involved in DNA substrate interactions and cleavage site determination. J Biol Chem. 2002 Jul 5;277(27):24659-66. Epub 2002 May 1. PMID:11986308 doi:http://dx.doi.org/10.1074/jbc.M111941200
↑ Guo Z, Qian L, Liu R, Dai H, Zhou M, Zheng L, Shen B. Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair. Mol Cell Biol. 2008 Jul;28(13):4310-9. doi: 10.1128/MCB.00200-08. Epub 2008 Apr, 28. PMID:18443037 doi:http://dx.doi.org/10.1128/MCB.00200-08
↑ Guo Z, Zheng L, Xu H, Dai H, Zhou M, Pascua MR, Chen QM, Shen B. Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding. Nat Chem Biol. 2010 Oct;6(10):766-73. doi: 10.1038/nchembio.422. Epub 2010 Aug, 22. PMID:20729856 doi:http://dx.doi.org/10.1038/nchembio.422
↑ de Barros AC, Takeda AA, Chang CW, Kobe B, Fontes MR. Structural basis of nuclear import of flap endonuclease 1 (FEN1). Acta Crystallogr D Biol Crystallogr. 2012 Jul;68(Pt 7):743-50. doi:, 10.1107/S0907444912010281. Epub 2012 Jun 15. PMID:22751659 doi:http://dx.doi.org/10.1107/S0907444912010281

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3uvu"

@@ Line 1: / Line 1: @@
 ==Structural basis of nuclear import of Flap endonuclease 1 (FEN1)==
 <StructureSection load='3uvu' size='340' side='right' caption='[[3uvu]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3uvu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UVU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3uvu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UVU FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pjn|1pjn]], [[3rzx|3rzx]], [[1pjm|1pjm]], [[3rz9|3rz9]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kpna2, Rch1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kpna2, Rch1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3uvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uvu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uvu RCSB], [http://www.ebi.ac.uk/pdbsum/3uvu PDBsum]</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=3uvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uvu OCA], [http://pdbe.org/3uvu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uvu RCSB], [http://www.ebi.ac.uk/pdbsum/3uvu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uvu ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3uvu" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Barros, A C]]
 [[Category: Fontes, M R.M]]

3uvu

From Proteopedia

Revision as of 07:51, 5 August 2016

Structural basis of nuclear import of Flap endonuclease 1 (FEN1)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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