2hzc: Difference between revisions

[[Image:2hzc.gif|left|200px]]<br /><applet load="2hzc" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

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].  

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: Kielkopf, C L.]]

[[Category: Sickmier, E A.]]

[[Category: Thickman, K R.]]

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