2m41

From Proteopedia

(Difference between revisions)

Current revision

Solution Structure of the AXH domain of Ataxin-1 in complex with ligand peptide from Capicua

Structural highlights

2m41 is a 2 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

CIC_HUMAN Transcriptional repressor which may play a role in development of the central nervous system (CNS).^[1]

Publication Abstract from PubMed

A main challenge for structural biologists is to understand the mechanisms that discriminate between molecular interactions and determine function. Here, we show how partner recognition of the AXH domain of the transcriptional co-regulator ataxin-1 is fine-tuned by a subtle balance between self- and hetero-associations. Ataxin-1 is the protein responsible for the hereditary spinocerebellar ataxia type 1, a disease linked to protein aggregation and transcriptional dysregulation. Expansion of a polyglutamine tract is essential for ataxin-1 aggregation, but the sequence-wise distant AXH domain plays an important aggravating role in the process. The AXH domain is also a key element for non-aberrant function as it intervenes in interactions with multiple protein partners. Previous data have shown that AXH is dimeric in solution and forms a dimer of dimers when crystallized. By solving the structure of a complex of AXH with a peptide from the interacting transcriptional repressor CIC, we show that the dimer interface of AXH is displaced by the new interaction and that, when blocked by the CIC peptide AXH aggregation and misfolding are impaired. This is a unique example in which palindromic self- and hetero-interactions within a sequence with chameleon properties discriminate the partner. We propose a drug design strategy for the treatment of SCA1 that is based on the information gained from the AXH/CIC complex.

Protein-protein interactions as a strategy towards protein-specific drug design: the example of ataxin-1.,de Chiara C, Menon RP, Kelly G, Pastore A PLoS One. 2013 Oct 14;8(10):e76456. doi: 10.1371/journal.pone.0076456. PMID:24155902^[2]

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

References

↑ Lee CJ, Chan WI, Cheung M, Cheng YC, Appleby VJ, Orme AT, Scotting PJ. CIC, a member of a novel subfamily of the HMG-box superfamily, is transiently expressed in developing granule neurons. Brain Res Mol Brain Res. 2002 Oct 15;106(1-2):151-6. PMID:12393275
↑ de Chiara C, Menon RP, Kelly G, Pastore A. Protein-protein interactions as a strategy towards protein-specific drug design: the example of ataxin-1. PLoS One. 2013 Oct 14;8(10):e76456. doi: 10.1371/journal.pone.0076456. PMID:24155902 doi:http://dx.doi.org/10.1371/journal.pone.0076456

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m41"

Categories: Homo sapiens | Large Structures | Kelly G | Pastore A | De Chiara C

@@ Line 1: / Line 1: @@
 ==Solution Structure of the AXH domain of Ataxin-1 in complex with ligand peptide from Capicua==
-<StructureSection load='2m41' size='340' side='right'caption='[[2m41]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
+<StructureSection load='2m41' size='340' side='right'caption='[[2m41]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2m41]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M41 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2m41]] is a 2 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=2M41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M41 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1oa8|1oa8]], [[1v06|1v06]]</div></td></tr>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATXN1, ATX1, SCA1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2m41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m41 OCA], [https://pdbe.org/2m41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m41 RCSB], [https://www.ebi.ac.uk/pdbsum/2m41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m41 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[https://www.uniprot.org/uniprot/ATX1_HUMAN ATX1_HUMAN]] Spinocerebellar ataxia type 1. Defects in ATXN1 are the cause of spinocerebellar ataxia type 1 (SCA1) [MIM:[https://omim.org/entry/164400 164400]]; also known as olivopontocerebellar atrophy I (OPCA I or OPCA1). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA1 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA1 is caused by expansion of a CAG repeat in the coding region of ATXN1. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7951322</ref> <ref>PMID:8634720</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/CIC_HUMAN CIC_HUMAN]] Transcriptional repressor which may play a role in development of the central nervous system (CNS).<ref>PMID:12393275</ref>  [[https://www.uniprot.org/uniprot/ATX1_HUMAN ATX1_HUMAN]] Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression. Binds RNA in vitro. May be involved in RNA metabolism. The expansion of the polyglutamine tract may alter this function.<ref>PMID:21475249</ref>
+[https://www.uniprot.org/uniprot/CIC_HUMAN CIC_HUMAN] Transcriptional repressor which may play a role in development of the central nervous system (CNS).<ref>PMID:12393275</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chiara, C de]]
+[[Category: Kelly G]]
-[[Category: Kelly, G]]
+[[Category: Pastore A]]
-[[Category: Pastore, A]]
+[[Category: De Chiara C]]
-[[Category: Ataxin-1 axh-cic complex]]
-[[Category: Protein/protein]]
-[[Category: Transcription regulator]]

2m41

From Proteopedia

Current revision

Solution Structure of the AXH domain of Ataxin-1 in complex with ligand peptide from Capicua

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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