OCA at 09:52, 18 March 2020

OCA — Wed, 18 Mar 2020 09:52:12 GMT

←Older revision		Revision as of 09:52, 18 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6sm2 is ~~ON HOLD until Paper~~ Publication	+	==Mutant immunoglobulin light chain causing amyloidosis (Pat-1)==
		+	<StructureSection load='6sm2' size='340' side='right'caption='[[6sm2]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6sm2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SM2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SM2 FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6sm1\|6sm1]]</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=6sm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sm2 OCA], [http://pdbe.org/6sm2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sm2 RCSB], [http://www.ebi.ac.uk/pdbsum/6sm2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sm2 ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In systemic light chain amyloidosis, an overexpressed antibody light chain (LC) forms fibrils which deposit in organs and cause their failure. While it is well-established that mutations in the LC's VL domain are important prerequisites, the mechanisms which render a patient LC amyloidogenic are ill-defined. In this study, we performed an in-depth analysis of the factors and mutations responsible for the pathogenic transformation of a patient-derived lambda LC, by recombinantly expressing variants in E. coli. We show that proteolytic cleavage of the patient LC resulting in an isolated VL domain is essential for fibril formation. Out of 11 mutations in the patient VL, only one, a leucine to valine mutation, is responsible for fibril formation. It disrupts a hydrophobic network rendering the C-terminal segment of VL more dynamic and decreasing domain stability. Thus, the combination of proteolytic cleavage and the destabilizing mutation trigger conformational changes that turn the LC pathogenic.

-	~~Authors:~~ Kazman, P., Vielberg, ~~M.-T.,~~ Cendales~~, M.D.P.~~, Hunziger, L., Weber, B., Hegenbart, U., Zacharias, M~~., Koehler~~, R~~., Schoenland~~, S., Groll, M., Buchner, J.	+	Fatal amyloid formation in a patient's antibody light chain is caused by a single point mutation.,Kazman P, Vielberg MT, Pulido Cendales MD, Hunziger L, Weber B, Hegenbart U, Zacharias M, Kohler R, Schonland S, Groll M, Buchner J Elife. 2020 Mar 10;9. pii: 52300. doi: 10.7554/eLife.52300. PMID:32151314<ref>PMID:32151314</ref>

-	~~Description: Mutant immunoglobulin light chain causing amyloidosis (Pat~~-1)	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6sm2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Buchner, J]]
		+	[[Category: Cendales, M D.P]]
		+	[[Category: Groll, M]]
	[[Category: Hegenbart, U]]		[[Category: Hegenbart, U]]
-	[[Category: Vielberg, M.-T]]
-	[[Category: Schoenland, S]]
-	[[Category: Kazman, P]]
	[[Category: Hunziger, L]]		[[Category: Hunziger, L]]
-	[[Category: ~~Zacharias~~, ~~M]]~~	+	[[Category: Kazman, P]]
-	~~[[Category: Groll, M~~]]	+
	[[Category: Koehler, R]]		[[Category: Koehler, R]]
		+	[[Category: Schoenland, S]]
		+	[[Category: Vielberg, M T]]
	[[Category: Weber, B]]		[[Category: Weber, B]]
-	[[Category: ~~Cendales~~, M~~.D.P~~]]	+	[[Category: Zacharias, M]]
-	[[Category: ~~Buchner, J~~]]	+	[[Category: Al amyloidosis]]
		+	[[Category: Antibody folding]]
		+	[[Category: Dynamic]]
		+	[[Category: Protein fibril]]
		+	[[Category: Protein stability]]

OCA: Protected "6sm2" [edit=sysop:move=sysop]

OCA — Wed, 28 Aug 2019 13:56:48 GMT

Protected "6sm2" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:56, 28 August 2019

OCA: New page: '''Unreleased structure''' The entry 6sm2 is ON HOLD until Paper Publication Authors: Kazman, P., Vielberg, M.-T., Cendales, M.D.P., Hunziger, L., Weber, B., Hegenbart, U., Zacharias, M...

OCA — Wed, 28 Aug 2019 13:56:46 GMT

New page: '''Unreleased structure''' The entry 6sm2 is ON HOLD until Paper Publication Authors: Kazman, P., Vielberg, M.-T., Cendales, M.D.P., Hunziger, L., Weber, B., Hegenbart, U., Zacharias, M...

New page

'''Unreleased structure'''

The entry 6sm2 is ON HOLD until Paper Publication

Authors: Kazman, P., Vielberg, M.-T., Cendales, M.D.P., Hunziger, L., Weber, B., Hegenbart, U., Zacharias, M., Koehler, R., Schoenland, S., Groll, M., Buchner, J.

Description: Mutant immunoglobulin light chain causing amyloidosis (Pat-1)
[[Category: Unreleased Structures]]
[[Category: Hegenbart, U]]
[[Category: Vielberg, M.-T]]
[[Category: Schoenland, S]]
[[Category: Kazman, P]]
[[Category: Hunziger, L]]
[[Category: Zacharias, M]]
[[Category: Groll, M]]
[[Category: Koehler, R]]
[[Category: Weber, B]]
[[Category: Cendales, M.D.P]]
[[Category: Buchner, J]]

6sm2 - Revision history

OCA at 09:52, 18 March 2020

OCA: Protected "6sm2" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6sm2 is ON HOLD until Paper Publication Authors: Kazman, P., Vielberg, M.-T., Cendales, M.D.P., Hunziger, L., Weber, B., Hegenbart, U., Zacharias, M...