|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of Kelch domain of the human NS1 binding protein== | | ==Crystal structure of Kelch domain of the human NS1 binding protein== |
| - | <StructureSection load='6n3h' size='340' side='right' caption='[[6n3h]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='6n3h' size='340' side='right'caption='[[6n3h]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n3h]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N3H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N3H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n3h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N3H FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IVNS1ABP, ARA3, FLARA3, KIAA0850, KLHL39, NS1, NS1BP, HSPC068 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6n3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n3h OCA], [http://pdbe.org/6n3h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n3h RCSB], [http://www.ebi.ac.uk/pdbsum/6n3h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n3h ProSAT]</span></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=6n3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n3h OCA], [https://pdbe.org/6n3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n3h RCSB], [https://www.ebi.ac.uk/pdbsum/6n3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n3h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NS1BP_HUMAN NS1BP_HUMAN]] Plays a role in cell division and in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats. Protects cells from cell death induced by actin destabilization; Protects neurons from dendritic spines and actin filaments damage induced by the actin-destabilizing cytochalasin B when overexpressed. Activates Erk signaling pathway when overexpressed in cultured cell lines (By similarity). May be a component of the cellular splicing machinery with a role in pre-mRNA splicing; may mediate the inhibition of splicing by NS/influenza virus NS1A protein. Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription.<ref>PMID:16582008</ref> | + | [https://www.uniprot.org/uniprot/NS1BP_HUMAN NS1BP_HUMAN] Plays a role in cell division and in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats. Protects cells from cell death induced by actin destabilization; Protects neurons from dendritic spines and actin filaments damage induced by the actin-destabilizing cytochalasin B when overexpressed. Activates Erk signaling pathway when overexpressed in cultured cell lines (By similarity). May be a component of the cellular splicing machinery with a role in pre-mRNA splicing; may mediate the inhibition of splicing by NS/influenza virus NS1A protein. Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription.<ref>PMID:16582008</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chook, Y M]] | + | [[Category: Large Structures]] |
| - | [[Category: Fontoura, B M.A]] | + | [[Category: Chook YM]] |
| - | [[Category: Padavannil, A]] | + | [[Category: Fontoura BMA]] |
| - | [[Category: Shang, G]] | + | [[Category: Padavannil A]] |
| - | [[Category: Zhang, K]] | + | [[Category: Shang G]] |
| - | [[Category: Mrna export]]
| + | [[Category: Zhang K]] |
| - | [[Category: Mrna splicing]]
| + | |
| - | [[Category: Splicing]]
| + | |
| Structural highlights
Function
NS1BP_HUMAN Plays a role in cell division and in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats. Protects cells from cell death induced by actin destabilization; Protects neurons from dendritic spines and actin filaments damage induced by the actin-destabilizing cytochalasin B when overexpressed. Activates Erk signaling pathway when overexpressed in cultured cell lines (By similarity). May be a component of the cellular splicing machinery with a role in pre-mRNA splicing; may mediate the inhibition of splicing by NS/influenza virus NS1A protein. Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription.[1]
Publication Abstract from PubMed
The influenza virulence factor NS1 protein interacts with the cellular NS1-BP protein to promote splicing and nuclear export of the viral M mRNAs. The viral M1 mRNA encodes the M1 matrix protein and is alternatively spliced into the M2 mRNA, which is translated into the M2 ion channel. These proteins have key functions in viral trafficking and budding. To uncover the NS1-BP structural and functional activities in splicing and nuclear export, we performed proteomics analysis of nuclear NS1-BP binding partners and showed its interaction with constituents of the splicing and mRNA export machineries. NS1-BP BTB domains form dimers in the crystal. Full-length NS1-BP is a dimer in solution and forms at least a dimer in cells. Mutations suggest that dimerization is important for splicing. The central BACK domain of NS1-BP interacts directly with splicing factors such as hnRNP K and PTBP1 and with the viral NS1 protein. The BACK domain is also the site for interactions with mRNA export factor Aly/REF and is required for viral M mRNA nuclear export. The crystal structure of the C-terminal Kelch domain shows that it forms a beta-propeller fold, which is required for the splicing function of NS1-BP. This domain interacts with the polymerase II C-terminal domain and SART1, which are involved in recruitment of splicing factors and spliceosome assembly, respectively. NS1-BP functions are not only critical for processing a subset of viral mRNAs but also impact levels and nuclear export of a subset of cellular mRNAs encoding factors involved in metastasis and immunity.
Structural-functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression.,Zhang K, Shang G, Padavannil A, Wang J, Sakthivel R, Chen X, Kim M, Thompson MG, Garcia-Sastre A, Lynch KW, Chen ZJ, Chook YM, Fontoura BMA Proc Natl Acad Sci U S A. 2018 Dec 11. pii: 1818012115. doi:, 10.1073/pnas.1818012115. PMID:30538201[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dunham EE, Stevens EA, Glover E, Bradfield CA. The aryl hydrocarbon receptor signaling pathway is modified through interactions with a Kelch protein. Mol Pharmacol. 2006 Jul;70(1):8-15. Epub 2006 Mar 31. PMID:16582008 doi:http://dx.doi.org/mol.106.024380
- ↑ Zhang K, Shang G, Padavannil A, Wang J, Sakthivel R, Chen X, Kim M, Thompson MG, Garcia-Sastre A, Lynch KW, Chen ZJ, Chook YM, Fontoura BMA. Structural-functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression. Proc Natl Acad Sci U S A. 2018 Dec 11. pii: 1818012115. doi:, 10.1073/pnas.1818012115. PMID:30538201 doi:http://dx.doi.org/10.1073/pnas.1818012115
|
