|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5c9k' size='340' side='right'caption='[[5c9k]], [[Resolution|resolution]] 1.92Å' scene=''> | | <StructureSection load='5c9k' size='340' side='right'caption='[[5c9k]], [[Resolution|resolution]] 1.92Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5c9k]] is a 8 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=5C9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C9K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5c9k]] is a 8 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=5C9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C9K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3b5g|3b5g]], [[3bdx|3bdx]]</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=5c9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c9k OCA], [https://pdbe.org/5c9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c9k RCSB], [https://www.ebi.ac.uk/pdbsum/5c9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c9k ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VL GENE SEGMENT 6A AND JL2/3 GENE SEGMENT ([http://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=5c9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c9k OCA], [http://pdbe.org/5c9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c9k RCSB], [http://www.ebi.ac.uk/pdbsum/5c9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5c9k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q96JD1_HUMAN Q96JD1_HUMAN] |
| - | Systemic amyloid light-chain (LC) amyloidosis is a disease process characterized by the pathological deposition of monoclonal LCs in tissue. All LC subtypes are capable of fibril formation although lambda chains, particularly those belonging to the lambda6 type, are overrepresented. Here, we report the thermodynamic and in vitro fibrillogenic properties of several mutants of the lambda6 protein 6aJL2 in which Pro7 and/or His8 was substituted by Ser or Pro. The H8P and H8S mutants were almost as stable as the wild-type protein and were poorly fibrillogenic. In contrast, the P7S mutation decreased the thermodynamic stability of 6aJL2 and greatly enhanced its capacity to form amyloid-like fibrils in vitro. The crystal structure of the P7S mutant showed that the substitution induced both local and long-distance effects, such as the rearrangement of the V(L) (variable region of the light chain)-V(L) interface. This mutant crystallized in two orthorhombic polymorphs, P2(1)2(1)2(1) and C222(1). In the latter, a monomer that was not arranged in the typical Bence-Jones dimer was observed for the first time. Crystal-packing analysis of the C222(1) lattice showed the establishment of intermolecular beta-beta interactions that involved the N-terminus and beta-strand B and that these could be relevant in the mechanism of LC fibril formation. Our results strongly suggest that Pro7 is a key residue in the conformation of the N-terminal sheet switch motif and, through long-distance interactions, is also critically involved in the contacts that stabilized the V(L) interface in lambda6 LCs.
| + | |
| - | | + | |
| - | A single mutation at the sheet switch region results in conformational changes favoring lambda6 light-chain fibrillogenesis.,Hernandez-Santoyo A, del Pozo Yauner L, Fuentes-Silva D, Ortiz E, Rudino-Pinera E, Sanchez-Lopez R, Horjales E, Becerril B, Rodriguez-Romero A J Mol Biol. 2010 Feb 19;396(2):280-92. Epub 2009 Nov 24. PMID:19941869<ref>PMID:19941869</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5c9k" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Becerril-Lujan, B]] | + | [[Category: Becerril-Lujan B]] |
| - | [[Category: Hernandez-Santoyo, A]] | + | [[Category: Hernandez-Santoyo A]] |
| - | [[Category: Luna-Martinez, O D]] | + | [[Category: Luna-Martinez OD]] |
| - | [[Category: Rodriguez-Romero, A]] | + | [[Category: Rodriguez-Romero A]] |
| - | [[Category: Al amyloidosis]]
| + | |
| - | [[Category: Beta-sandwich]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunoglobulin]]
| + | |
| - | [[Category: Lambda vi subgroup]]
| + | |
