@article {2017|2036,
	title = {VLITL is a major cross-β-sheet signal for fibrinogen Aα-chain frameshift variants.},
	journal = {Blood},
	volume = {130},
	year = {2017},
	month = {2017 12 21},
	pages = {2799-2807},
	abstract = {<p>The first case of hereditary fibrinogen Aα-chain amyloidosis was recognized \&gt;20 years ago, but disease mechanisms still remain unknown. Here we report detailed clinical and proteomics studies of a French kindred with a novel amyloidogenic fibrinogen Aα-chain frameshift variant, Phe521Leufs, causing a severe familial form of renal amyloidosis. Next, we focused our investigations to elucidate the molecular basis that render this Aα-chain variant amyloidogenic. We show that a 49-mer peptide derived from the C-terminal part of the Phe521Leufs chain is deposited as fibrils in the patient\&$\#$39;s kidneys, establishing that only a small portion of Phe521Leufs directly contributes to amyloid formation in vivo. In silico analysis indicated that this 49-mer Aα-chain peptide contained a motif (VLITL), with a high intrinsic propensity for β-aggregation at residues 44 to 48 of human renal fibrils. To experimentally verify the amyloid propensity of VLITL, we generated synthetic Phe521Leufs-derived peptides and compared their capacity for fibril formation in vitro with that of their VLITL-deleted counterparts. We show that VLITL forms typical amyloid fibrils in vitro and is a major signal for cross-β-sheet self-association of the 49-mer Phe521Leufs peptide identified in vivo, whereas its absence abrogates fibril formation. This study provides compelling evidence that VLITL confers amyloidogenic properties to Aα-chain frameshift variants, yielding a previously unknown molecular basis for the pathogenesis of Aα-chain amyloidosis.</p>
},
	keywords = {Amino Acid Motifs, Amino Acid Sequence, Amyloid, Amyloidosis, Familial, Fibrinogen, Frameshift Mutation, Humans, Kidney, Protein Conformation, beta-Strand},
	issn = {1528-0020},
	doi = {10.1182/blood-2017-07-796185},
	author = {Garnier, Cyrille and Briki, Fatma and Nedelec, Brigitte and Le Pogamp, Patrick and Dogan, Ahmet and Rioux-Leclercq, Nathalie and Goude, Renan and Beugnet, Caroline and Martin, Laurent and Delpech, Marc and Bridoux, Frank and Grateau, Gilles and Doucet, Jean and Philippe Derreumaux and Valleix, Sophie}
}
@article {2009|2009,
	title = {Structural diversity of the soluble trimers of the human amylin(20-29) peptide revealed by molecular dynamics simulations},
	journal = {J. Chem. Phys.},
	volume = {130},
	number = {12},
	year = {2009},
	month = {mar},
	pages = {125101},
	keywords = {Amino Acid Sequence, Amyloid, Humans, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Protein Multimerization, Protein Structure, Quaternary, Solubility, Solvents},
	doi = {10.1063/1.3097982},
	author = {Mo, Yuxiang and Lu, Yan and Wei, Guanghong and Philippe Derreumaux}
}
