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==Structure of the W64R amyloidogenic variant of human lysozyme==
<StructureSection load='7ap7' size='340' side='right'caption='[[7ap7]], [[Resolution|resolution]] 1.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AP7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AP7 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]] 1.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7ap7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ap7 OCA], [https://pdbe.org/7ap7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ap7 RCSB], [https://www.ebi.ac.uk/pdbsum/7ap7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ap7 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The accumulation in vital organs of amyloid fibrils made of mutational variants of lysozyme (HuL) is associated with a human systemic amyloid disease. The detailed comparison of the in vitro properties of the I56T and D67H amyloidogenic variants to those of the T70N non-amyloidogenic variant and the wild-type (WT) protein suggested that the deposition of large amounts of aggregated disease-related lysozyme variants is initiated by the formation of transient intermediate species. The ability to populate such intermediates is essentially due to the destabilisation of the protein and the loss of the global structural cooperativity under physiologically relevant conditions. Here, we report the characterisation of a third naturally occurring amyloidogenic lysozyme variant, W64R, in comparison with the I56T and WT proteins. The X-ray crystal structure of the W64R variant at 1.15 A resolution is very similar to that of the WT protein; a few interactions within the beta-domain and at the interface between the alpha- and beta-domains differ, however, from those in the WT protein. Consequently, the W64R mutation destabilizes the protein to an extent that is similar to that observed for the I56T and D67H mutations. The DeltaG degrees NU(H2O) is reduced by 24 kJ.mol(-1) and the Tm is about 12 degrees C lower than that of the WT protein. Under native conditions, the W64R and I56T proteins are readily digested by proteinase K, while the WT protein remains intact. These results suggest that the two variant proteins transiently populate similar partially unfolded states in which proteinase K cleavage sites are accessible to the protease. Moreover, the in vitro aggregation properties of the W64R protein are similar to those of the I56T variant. Altogether, these results indicate that the properties of the W64R protein are astonishingly similar to those of the I56T variant. They further corroborate the idea that HuL variants associated with the disease are those whose stability and global structural cooperativity are sufficiently reduced to allow the formation of aggregation prone partially folded intermediates under physiological conditions.

Characterisation of the structural, dynamic and aggregation properties of the W64R amyloidogenic variant of human lysozyme.,Vettore N, Moray J, Brans A, Herman R, Charlier P, Kumita JR, Kerff F, Dobson CM, Dumoulin M Biophys Chem. 2021 Apr;271:106563. doi: 10.1016/j.bpc.2021.106563. Epub 2021 Feb , 13. PMID:33640796<ref>PMID:33640796</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Lysozyme 3D structures|Lysozyme 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Brans A]]
[[Category: Charlier P]]
[[Category: Dobson C]]
[[Category: Dumoulin M]]
[[Category: Herman R]]
[[Category: Kerff F]]
[[Category: Kumita J]]
[[Category: Morray J]]
[[Category: Sauvage E]]
[[Category: Vettore N]]