2hzc

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(New page: 200px<br /> <applet load="2hzc" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hzc, resolution 1.47&Aring;" /> '''Crystal structure o...)
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<applet load="2hzc" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="2hzc, resolution 1.47&Aring;" />
caption="2hzc, resolution 1.47&Aring;" />
'''Crystal structure of the N-terminal RRM of the U2AF large subunit'''<br />
'''Crystal structure of the N-terminal RRM of the U2AF large subunit'''<br />
==Overview==
==Overview==
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The essential pre-mRNA splicing factor, U2 auxiliary factor 65KD, (U2AF(65)) recognizes the polypyrimidine tract (Py-tract) consensus, sequence of the pre-mRNA using two RNA recognition motifs (RRMs), the most, prevalent class of eukaryotic RNA-binding domain. The Py-tracts of higher, eukaryotic pre-mRNAs are often interrupted with purines, yet U2AF(65) must, identify these degenerate Py-tracts for accurate pre-mRNA splicing., Previously, the structure of a U2AF(65) variant in complex with poly(U), RNA suggested that rearrangement of flexible side-chains or bound water, molecules may contribute to degenerate Py-tract recognition by U2AF(65)., Here, the X-ray structure of the N-terminal RRM domain of U2AF(65) (RRM1), is described at 1.47 A resolution in the absence of RNA. Notably, RNA-binding by U2AF(65) selectively stabilizes pre-existing alternative, conformations of three side-chains located at the RNA interface (Arg150, Lys225, and Arg227). Additionally, a flexible loop connecting the, beta2/beta3 strands undergoes a conformational change to interact with the, RNA. These pre-existing alternative conformations may contribute to the, ability of U2AF(65) to recognize a variety of Py-tract sequences. This, rare, high-resolution view of an important member of the RRM class of, RNA-binding domains highlights the role of alternative side-chain, conformations in RNA recognition.
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The essential pre-mRNA splicing factor, U2 auxiliary factor 65KD (U2AF(65)) recognizes the polypyrimidine tract (Py-tract) consensus sequence of the pre-mRNA using two RNA recognition motifs (RRMs), the most prevalent class of eukaryotic RNA-binding domain. The Py-tracts of higher eukaryotic pre-mRNAs are often interrupted with purines, yet U2AF(65) must identify these degenerate Py-tracts for accurate pre-mRNA splicing. Previously, the structure of a U2AF(65) variant in complex with poly(U) RNA suggested that rearrangement of flexible side-chains or bound water molecules may contribute to degenerate Py-tract recognition by U2AF(65). Here, the X-ray structure of the N-terminal RRM domain of U2AF(65) (RRM1) is described at 1.47 A resolution in the absence of RNA. Notably, RNA-binding by U2AF(65) selectively stabilizes pre-existing alternative conformations of three side-chains located at the RNA interface (Arg150, Lys225, and Arg227). Additionally, a flexible loop connecting the beta2/beta3 strands undergoes a conformational change to interact with the RNA. These pre-existing alternative conformations may contribute to the ability of U2AF(65) to recognize a variety of Py-tract sequences. This rare, high-resolution view of an important member of the RRM class of RNA-binding domains highlights the role of alternative side-chain conformations in RNA recognition.
==About this Structure==
==About this Structure==
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2HZC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and P6G as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 2FZR. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HZC OCA].
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2HZC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=P6G:'>P6G</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 2FZR. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HZC OCA].
==Reference==
==Reference==
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Alternative Conformations at the RNA-binding Surface of the N-terminal U2AF(65) RNA Recognition Motif., Thickman KR, Sickmier EA, Kielkopf CL, J Mol Biol. 2007 Feb 23;366(3):703-10. Epub 2006 Dec 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17188295 17188295]
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Alternative conformations at the RNA-binding surface of the N-terminal U2AF(65) RNA recognition motif., Thickman KR, Sickmier EA, Kielkopf CL, J Mol Biol. 2007 Feb 23;366(3):703-10. Epub 2006 Dec 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17188295 17188295]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Kielkopf, C.L.]]
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[[Category: Kielkopf, C L.]]
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[[Category: Sickmier, E.A.]]
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[[Category: Sickmier, E A.]]
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[[Category: Thickman, K.R.]]
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[[Category: Thickman, K R.]]
[[Category: P6G]]
[[Category: P6G]]
[[Category: ZN]]
[[Category: ZN]]
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[[Category: rrm]]
[[Category: rrm]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:38:54 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:47:23 2008''

Revision as of 15:47, 21 February 2008


2hzc, resolution 1.47Å

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Crystal structure of the N-terminal RRM of the U2AF large subunit

Overview

The essential pre-mRNA splicing factor, U2 auxiliary factor 65KD (U2AF(65)) recognizes the polypyrimidine tract (Py-tract) consensus sequence of the pre-mRNA using two RNA recognition motifs (RRMs), the most prevalent class of eukaryotic RNA-binding domain. The Py-tracts of higher eukaryotic pre-mRNAs are often interrupted with purines, yet U2AF(65) must identify these degenerate Py-tracts for accurate pre-mRNA splicing. Previously, the structure of a U2AF(65) variant in complex with poly(U) RNA suggested that rearrangement of flexible side-chains or bound water molecules may contribute to degenerate Py-tract recognition by U2AF(65). Here, the X-ray structure of the N-terminal RRM domain of U2AF(65) (RRM1) is described at 1.47 A resolution in the absence of RNA. Notably, RNA-binding by U2AF(65) selectively stabilizes pre-existing alternative conformations of three side-chains located at the RNA interface (Arg150, Lys225, and Arg227). Additionally, a flexible loop connecting the beta2/beta3 strands undergoes a conformational change to interact with the RNA. These pre-existing alternative conformations may contribute to the ability of U2AF(65) to recognize a variety of Py-tract sequences. This rare, high-resolution view of an important member of the RRM class of RNA-binding domains highlights the role of alternative side-chain conformations in RNA recognition.

About this Structure

2HZC is a Single protein structure of sequence from Homo sapiens with and as ligands. This structure supersedes the now removed PDB entry 2FZR. Full crystallographic information is available from OCA.

Reference

Alternative conformations at the RNA-binding surface of the N-terminal U2AF(65) RNA recognition motif., Thickman KR, Sickmier EA, Kielkopf CL, J Mol Biol. 2007 Feb 23;366(3):703-10. Epub 2006 Dec 2. PMID:17188295

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