1rxv: Difference between revisions

Revision as of 15:55, 21 February 2008

Crystal Structure of A. Fulgidus FEN-1 bound to DNA

OverviewOverview

Flap EndoNuclease-1 (FEN-1) and the processivity factor proliferating cell nuclear antigen (PCNA) are central to DNA replication and repair. To clarify the molecular basis of FEN-1 specificity and PCNA activation, we report here structures of FEN-1:DNA and PCNA:FEN-1-peptide complexes, along with fluorescence resonance energy transfer (FRET) and mutational results. FEN-1 binds the unpaired 3' DNA end (3' flap), opens and kinks the DNA, and promotes conformational closing of a flexible helical clamp to facilitate 5' cleavage specificity. Ordering of unstructured C-terminal regions in FEN-1 and PCNA creates an intermolecular beta sheet interface that directly links adjacent PCNA and DNA binding regions of FEN-1 and suggests how PCNA stimulates FEN-1 activity. The DNA and protein conformational changes, composite complex structures, FRET, and mutational results support enzyme-PCNA alignments and a kinked DNA pivot point that appear suitable to coordinate rotary handoffs of kinked DNA intermediates among enzymes localized by the three PCNA binding sites.

About this StructureAbout this Structure

1RXV is a Single protein structure of sequence from Archaeoglobus fulgidus. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for FEN-1 substrate specificity and PCNA-mediated activation in DNA replication and repair., Chapados BR, Hosfield DJ, Han S, Qiu J, Yelent B, Shen B, Tainer JA, Cell. 2004 Jan 9;116(1):39-50. PMID:14718165

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OCA

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-[[Image:1rxv.gif|left|200px]]<br /><applet load="1rxv" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="1rxv, resolution 2.5&Aring;" />
 '''Crystal Structure of A. Fulgidus FEN-1 bound to DNA'''<br />
 ==Overview==
-Flap EndoNuclease-1 (FEN-1) and the processivity factor proliferating cell, nuclear antigen (PCNA) are central to DNA replication and repair. To, clarify the molecular basis of FEN-1 specificity and PCNA activation, we, report here structures of FEN-1:DNA and PCNA:FEN-1-peptide complexes, along with fluorescence resonance energy transfer (FRET) and mutational, results. FEN-1 binds the unpaired 3' DNA end (3' flap), opens and kinks, the DNA, and promotes conformational closing of a flexible helical clamp, to facilitate 5' cleavage specificity. Ordering of unstructured C-terminal, regions in FEN-1 and PCNA creates an intermolecular beta sheet interface, that directly links adjacent PCNA and DNA binding regions of FEN-1 and, suggests how PCNA stimulates FEN-1 activity. The DNA and protein, conformational changes, composite complex structures, FRET, and mutational, results support enzyme-PCNA alignments and a kinked DNA pivot point that, appear suitable to coordinate rotary handoffs of kinked DNA intermediates, among enzymes localized by the three PCNA binding sites.
+Flap EndoNuclease-1 (FEN-1) and the processivity factor proliferating cell nuclear antigen (PCNA) are central to DNA replication and repair. To clarify the molecular basis of FEN-1 specificity and PCNA activation, we report here structures of FEN-1:DNA and PCNA:FEN-1-peptide complexes, along with fluorescence resonance energy transfer (FRET) and mutational results. FEN-1 binds the unpaired 3' DNA end (3' flap), opens and kinks the DNA, and promotes conformational closing of a flexible helical clamp to facilitate 5' cleavage specificity. Ordering of unstructured C-terminal regions in FEN-1 and PCNA creates an intermolecular beta sheet interface that directly links adjacent PCNA and DNA binding regions of FEN-1 and suggests how PCNA stimulates FEN-1 activity. The DNA and protein conformational changes, composite complex structures, FRET, and mutational results support enzyme-PCNA alignments and a kinked DNA pivot point that appear suitable to coordinate rotary handoffs of kinked DNA intermediates among enzymes localized by the three PCNA binding sites.
 ==About this Structure==
-RXV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RXV OCA].
+RXV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RXV OCA].
 ==Reference==
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 [[Category: Archaeoglobus fulgidus]]
 [[Category: Single protein]]
-[[Category: Chapados, B.R.]]
+[[Category: Chapados, B R.]]
 [[Category: Han, S.]]
-[[Category: Hosfield, D.J.]]
+[[Category: Hosfield, D J.]]
 [[Category: Qiu, J.]]
 [[Category: Shen, B.]]
-[[Category: Tainer, J.A.]]
+[[Category: Tainer, J A.]]
 [[Category: Yelent, B.]]
 [[Category: 3' flap binding site]]
@@ Line 27: / Line 27: @@
 [[Category: protein-dna complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:56:32 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:55:41 2008''