3v30

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(Difference between revisions)

Revision as of 08:26, 20 July 2022

Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human RFXANK

Structural highlights

3v30 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	ANKRA1, RFXANK, RFXB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[RFXK_HUMAN] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry.^[1] ^[2] ^[3] [RFX5_HUMAN] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry.

Function

[RFXK_HUMAN] Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator (MHC2TA). May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters. Isoform RFX-B-delta5 is not involved in the positive regulation of MHC class II genes. [RFX5_HUMAN] Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters.

Publication Abstract from PubMed

Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). Crystal structures of the ankyrin repeat domain of ANKRA2 in complex with its binding peptides revealed that each of the middle three ankyrin repeats of ANKRA2 recognizes a residue from the PxLPxI/L motif in a tumbler-lock binding mode, with ANKRA2 acting as the lock and the linear binding motif serving as the key. Structural analysis showed that three disease-causing mutations in RFXANK affect residues that are critical for binding to RFX5. These results suggest a fundamental principle of longitudinal recognition of linear sequences by a repeat-type domain. In addition, phosphorylation of serine 350, a residue embedded within the PxLPxI/L motif of HDAC4, impaired the binding of ANKRA2 but generated a high-affinity docking site for 14-3-3 proteins, which may help sequester this HDAC in the cytoplasm. Thus, the binding preference of the PxLPxI/L motif is signal-dependent. Furthermore, proteome-wide screening suggested that a similar phosphorylation-dependent switch may operate in other pathways. Together, our findings uncover a previously uncharacterized sequence- and signal-dependent peptide recognition mode for a repeat-type protein domain.

Sequence-Specific Recognition of a PxLPxI/L Motif by an Ankyrin Repeat Tumbler Lock.,Xu C, Jin J, Bian C, Lam R, Tian R, Weist R, You L, Nie J, Bochkarev A, Tempel W, Tan CS, Wasney GA, Vedadi M, Gish GD, Arrowsmith CH, Pawson T, Yang XJ, Min J Sci Signal. 2012 May 29;5(226):ra39. PMID:22649097^[4]

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

References

↑ Masternak K, Barras E, Zufferey M, Conrad B, Corthals G, Aebersold R, Sanchez JC, Hochstrasser DF, Mach B, Reith W. A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients. Nat Genet. 1998 Nov;20(3):273-7. PMID:9806546 doi:http://dx.doi.org/10.1038/3081
↑ Nagarajan UM, Louis-Plence P, DeSandro A, Nilsen R, Bushey A, Boss JM. RFX-B is the gene responsible for the most common cause of the bare lymphocyte syndrome, an MHC class II immunodeficiency. Immunity. 1999 Feb;10(2):153-62. PMID:10072068
↑ Nagarajan UM, Peijnenburg A, Gobin SJ, Boss JM, van den elsen PJ. Novel mutations within the RFX-B gene and partial rescue of MHC and related genes through exogenous class II transactivator in RFX-B-deficient cells. J Immunol. 2000 Apr 1;164(7):3666-74. PMID:10725724
↑ Xu C, Jin J, Bian C, Lam R, Tian R, Weist R, You L, Nie J, Bochkarev A, Tempel W, Tan CS, Wasney GA, Vedadi M, Gish GD, Arrowsmith CH, Pawson T, Yang XJ, Min J. Sequence-Specific Recognition of a PxLPxI/L Motif by an Ankyrin Repeat Tumbler Lock. Sci Signal. 2012 May 29;5(226):ra39. PMID:22649097 doi:10.1126/scisignal.2002979

1 Structural highlights
2 Disease
3 Function
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/3v30"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human RFXANK==
-<StructureSection load='3v30' size='340' side='right' caption='[[3v30]], [[Resolution|resolution]] 1.57&Aring;' scene=''>
+<StructureSection load='3v30' size='340' side='right'caption='[[3v30]], [[Resolution|resolution]] 1.57&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3v30]] 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=3V30 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V30 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3v30]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V30 FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANKRA1, RFXANK, RFXB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANKRA1, RFXANK, RFXB ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3v30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v30 OCA], [http://pdbe.org/3v30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3v30 RCSB], [http://www.ebi.ac.uk/pdbsum/3v30 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3v30 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=3v30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v30 OCA], [https://pdbe.org/3v30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v30 RCSB], [https://www.ebi.ac.uk/pdbsum/3v30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v30 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/RFXK_HUMAN RFXK_HUMAN]] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9806546</ref> <ref>PMID:10072068</ref> <ref>PMID:10725724</ref>  [[http://www.uniprot.org/uniprot/RFX5_HUMAN RFX5_HUMAN]] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry.
+[[https://www.uniprot.org/uniprot/RFXK_HUMAN RFXK_HUMAN]] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9806546</ref> <ref>PMID:10072068</ref> <ref>PMID:10725724</ref>  [[https://www.uniprot.org/uniprot/RFX5_HUMAN RFX5_HUMAN]] Immunodeficiency by defective expression of HLA class 2. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/RFXK_HUMAN RFXK_HUMAN]] Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator (MHC2TA). May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters. Isoform RFX-B-delta5 is not involved in the positive regulation of MHC class II genes. [[http://www.uniprot.org/uniprot/RFX5_HUMAN RFX5_HUMAN]] Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters.
+[[https://www.uniprot.org/uniprot/RFXK_HUMAN RFXK_HUMAN]] Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator (MHC2TA). May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters. Isoform RFX-B-delta5 is not involved in the positive regulation of MHC class II genes. [[https://www.uniprot.org/uniprot/RFX5_HUMAN RFX5_HUMAN]] Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Arrowsmith, C H]]
 [[Category: Bian, C B]]

3v30

From Proteopedia

Revision as of 08:26, 20 July 2022

Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human RFXANK

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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