2hh2

From Proteopedia

(Difference between revisions)

Current revision

Solution structure of the fourth KH domain of KSRP

Structural highlights

2hh2 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FUBP2_HUMAN Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The AU-rich element (ARE) RNA-binding protein KSRP (K-homology splicing regulator protein) contains four KH domains and promotes the degradation of specific mRNAs that encode proteins with functions in cellular proliferation and inflammatory response. The fourth KH domain (KH4) is essential for mRNA recognition and decay but requires the third KH domain (KH3) for its function. We show that KH3 and KH4 behave as independent binding modules and can interact with different regions of the AU-rich RNA targets of KSRP. This provides KSRP with the structural flexibility needed to recognize a set of different targets in the context of their 3'UTR structural settings. Surprisingly, we find that KH4 binds to its target AREs with lower affinity than KH3 and that KSRP's mRNA binding, and mRNA degradation activities are closely associated with a conserved structural element of KH4.

The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation.,Garcia-Mayoral MF, Hollingworth D, Masino L, Diaz-Moreno I, Kelly G, Gherzi R, Chou CF, Chen CY, Ramos A Structure. 2007 Apr;15(4):485-98. PMID:17437720^[4]

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

References

↑ Min H, Turck CW, Nikolic JM, Black DL. A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer. Genes Dev. 1997 Apr 15;11(8):1023-36. PMID:9136930
↑ Davis-Smyth T, Duncan RC, Zheng T, Michelotti G, Levens D. The far upstream element-binding proteins comprise an ancient family of single-strand DNA-binding transactivators. J Biol Chem. 1996 Dec 6;271(49):31679-87. PMID:8940189
↑ Markovtsov V, Nikolic JM, Goldman JA, Turck CW, Chou MY, Black DL. Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol Cell Biol. 2000 Oct;20(20):7463-79. PMID:11003644
↑ Garcia-Mayoral MF, Hollingworth D, Masino L, Diaz-Moreno I, Kelly G, Gherzi R, Chou CF, Chen CY, Ramos A. The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation. Structure. 2007 Apr;15(4):485-98. PMID:17437720 doi:http://dx.doi.org/10.1016/j.str.2007.03.006

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hh2"

Categories: Homo sapiens | Large Structures | Garcia-Mayoral MF

@@ Line 1: / Line 1: @@
-[[Image:2hh2.jpg|left|200px]]<br /><applet load="2hh2" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2hh2" />
-'''Solution structure of the fourth KH domain of KSRP'''<br />
-==Overview==
+==Solution structure of the fourth KH domain of KSRP==
-The AU-rich element (ARE) RNA-binding protein KSRP (K-homology splicing, regulator protein) contains four KH domains and promotes the degradation, of specific mRNAs that encode proteins with functions in cellular, proliferation and inflammatory response. The fourth KH domain (KH4) is, essential for mRNA recognition and decay but requires the third KH domain, (KH3) for its function. We show that KH3 and KH4 behave as independent, binding modules and can interact with different regions of the AU-rich RNA, targets of KSRP. This provides KSRP with the structural flexibility needed, to recognize a set of different targets in the context of their 3'UTR, structural settings. Surprisingly, we find that KH4 binds to its target, AREs with lower affinity than KH3 and that KSRP's mRNA binding, and mRNA, degradation activities are closely associated with a conserved structural, element of KH4.
+<StructureSection load='2hh2' size='340' side='right'caption='[[2hh2]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2hh2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HH2 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2hh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hh2 OCA], [https://pdbe.org/2hh2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hh2 RCSB], [https://www.ebi.ac.uk/pdbsum/2hh2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hh2 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/FUBP2_HUMAN FUBP2_HUMAN] Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.<ref>PMID:9136930</ref> <ref>PMID:8940189</ref> <ref>PMID:11003644</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hh/2hh2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hh2 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The AU-rich element (ARE) RNA-binding protein KSRP (K-homology splicing regulator protein) contains four KH domains and promotes the degradation of specific mRNAs that encode proteins with functions in cellular proliferation and inflammatory response. The fourth KH domain (KH4) is essential for mRNA recognition and decay but requires the third KH domain (KH3) for its function. We show that KH3 and KH4 behave as independent binding modules and can interact with different regions of the AU-rich RNA targets of KSRP. This provides KSRP with the structural flexibility needed to recognize a set of different targets in the context of their 3'UTR structural settings. Surprisingly, we find that KH4 binds to its target AREs with lower affinity than KH3 and that KSRP's mRNA binding, and mRNA degradation activities are closely associated with a conserved structural element of KH4.
-==About this Structure==
+The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation.,Garcia-Mayoral MF, Hollingworth D, Masino L, Diaz-Moreno I, Kelly G, Gherzi R, Chou CF, Chen CY, Ramos A Structure. 2007 Apr;15(4):485-98. PMID:17437720<ref>PMID:17437720</ref>
-HH2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HH2 OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation., Garcia-Mayoral MF, Hollingworth D, Masino L, Diaz-Moreno I, Kelly G, Gherzi R, Chou CF, Chen CY, Ramos A, Structure. 2007 Apr;15(4):485-98. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17437720 17437720]
+</div>
+<div class="pdbe-citations 2hh2" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Garcia-Mayoral, M.F.]]
+[[Category: Garcia-Mayoral MF]]
-[[Category: kh-rna binding domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:46:00 2007''

2hh2

From Proteopedia

Current revision

Solution structure of the fourth KH domain of KSRP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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