6e4y: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Anti-PCSK9 fab 6E2 bound to the N-terminal peptide from PCSK9, unmodified== | |||
<StructureSection load='6e4y' size='340' side='right'caption='[[6e4y]], [[Resolution|resolution]] 2.24Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6e4y]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E4Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E4Y FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.24Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NEP:N1-PHOSPHONOHISTIDINE'>NEP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6e4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e4y OCA], [https://pdbe.org/6e4y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e4y RCSB], [https://www.ebi.ac.uk/pdbsum/6e4y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e4y ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A097PUG4_MOUSE A0A097PUG4_MOUSE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Proprotein convertase subtilisin/kexin 9 (PCSK9) is a key regulator of lipid metabolism by degrading liver LDL receptors. Structural studies have provided molecular details of PCSK9 function. However, the N-terminal acidic stretch of the PCSK9 prodomain (Q31-T60) has eluded structural investigation, since it is in a disordered state. The interest in this region is intensified by the presence of human missense mutations associated with low and high LDL-c levels (E32K, D35Y, and R46L, respectively), as well as two posttranslationally modified sites, sulfated Y38 and phosphorylated S47. Herein we show that a segment within this region undergoes disorder-to-order transition. Experiments with acidic stretch-derived peptides demonstrated that the folding is centered at the segment Y38-L45, which adopts an alpha-helix as determined by NMR analysis of free peptides and by X-ray crystallography of peptides in complex with antibody 6E2 (Ab6E2). In the Fab6E2-peptide complexes, the structured region features a central 2 1/4-turn alpha-helix and encompasses up to 2/3 of the length of the acidic stretch, including the missense mutations and posttranslationally modified sites. Experiments with helix-breaking proline substitutions in peptides and in PCSK9 protein indicated that Ab6E2 specifically recognizes the helical conformation of the acidic stretch. Therefore, the observed quantitative binding of Ab6E2 to native PCSK9 from various cell lines suggests that the disorder-to-order transition is a true feature of PCSK9 and not limited to peptides. Because the helix provides a constrained spatial orientation of the missense mutations and the posttranslationally modified residues, it is probable that their biological functions take place in the context of an ordered conformational state. | |||
Identification of a Helical Segment within the Intrinsically Disordered Region of the PCSK9 Prodomain.,Ultsch M, Li W, Eigenbrot C, Di Lello P, Lipari MT, Gerhardy S, AhYoung AP, Quinn J, Franke Y, Chen Y, Kong Beltran M, Peterson A, Kirchhofer D J Mol Biol. 2019 Mar 1;431(5):885-903. doi: 10.1016/j.jmb.2018.11.025. Epub 2019 , Jan 15. PMID:30653992<ref>PMID:30653992</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6e4y" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[PCSK9|PCSK9]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Kirchhofer DK]] | |||
[[Category: Ultsch MH]] | |||