3v31: Difference between revisions
No edit summary |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human ANKRA2== | ==Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human ANKRA2== | ||
<StructureSection load='3v31' size='340' side='right' caption='[[3v31]], [[Resolution|resolution]] 1.57Å' scene=''> | <StructureSection load='3v31' size='340' side='right'caption='[[3v31]], [[Resolution|resolution]] 1.57Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3v31]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3v31]] 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=3V31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V31 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.57Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=3v31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v31 OCA], [https://pdbe.org/3v31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v31 RCSB], [https://www.ebi.ac.uk/pdbsum/3v31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v31 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ANRA2_HUMAN ANRA2_HUMAN] May facilitate endocytosis by linking megalin to components of the cytoskeleton or endocytic machinery. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 28: | Line 23: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith CH]] | ||
[[Category: Bian | [[Category: Bian CB]] | ||
[[Category: Bochkarev | [[Category: Bochkarev A]] | ||
[[Category: Bountra | [[Category: Bountra C]] | ||
[[Category: Edwards | [[Category: Edwards AM]] | ||
[[Category: Kania | [[Category: Kania J]] | ||
[[Category: Lam | [[Category: Lam R]] | ||
[[Category: Min | [[Category: Min J]] | ||
[[Category: Weigelt J]] | |||
[[Category: Weigelt | [[Category: Xu C]] | ||
[[Category: Xu | |||
Latest revision as of 05:32, 21 November 2024
Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human ANKRA2Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human ANKRA2
Structural highlights
FunctionANRA2_HUMAN May facilitate endocytosis by linking megalin to components of the cytoskeleton or endocytic machinery. Publication Abstract from PubMedAnkyrin 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||