Journal ArticleDOI
Inherent biophysical properties modulate the toxicity of soluble amyloidogenic light chains
Martina Maritan,Margherita Romeo,Luca Oberti,Pietro Sormanni,Masayoshi Tasaki,Rosaria Russo,Arianna Ambrosetti,Paolo Motta,Paola Rognoni,Giulia Mazzini,Alberto Barbiroli,Giovanni Palladini,Michele Vendruscolo,Luisa Diomede,Martino Bolognesi,Giampaolo Merlini,Francesca Lavatelli,Stefano Ricagno +17 more
Reads0
Chats0
TLDR
The results of this study show a strong correlation between the overall conformational properties of the native fold and the proteotoxicity of cardiotropic LCs, and a comparison of H6 and mH6 shows closely matching crystal structures.About:
This article is published in Journal of Molecular Biology.The article was published on 2020-02-14. It has received 22 citations till now. The article focuses on the topics: Proteotoxicity & Protein structure.read more
Citations
More filters
Journal ArticleDOI
Mass spectrometry characterization of light chain fragmentation sites in cardiac AL amyloidosis:insights into the timing of proteolysis.
Francesca Lavatelli,Giulia Mazzini,Stefano Ricagno,Federica Iavarone,Paola Rognoni,Paolo Milani,Mario Nuvolone,Paolo Swuec,Serena Caminito,Masayoshi Tasaki,Antonio Chaves-Sanjuan,Andrea Urbani,Andrea Urbani,Giampaolo Merlini,Giovanni Palladini +14 more
TL;DR: Although the data do not exclude that proteolysis of native LC dimers may destabilize their structure and favor fibril formation, the data show that LC deposition largely precedes the proteolytic events documentable in mature AL fibrils.
Journal ArticleDOI
Molecular mechanism of amyloidogenic mutations in hypervariable regions of antibody light chains.
Georg J. Rottenaicher,Benedikt Weber,Florian Rührnößl,Pamina Kazman,Ramona M. Absmeier,Manuel Hitzenberger,Martin Zacharias,Johannes Buchner +7 more
TL;DR: In this paper, the authors compare a patient VL domain with its nonamyloidogenic germline counterpart and show that, out of the five mutations present, two of them strongly destabilize the protein and induce amyloid fibril formation.
Journal ArticleDOI
How I treat AL amyloidosis
TL;DR: The treatment of patients with systemic light chain (AL) amyloidosis is a challenge to hematologists as discussed by the authors , and the availability of new effective drugs allows to better personalize the therapy, reduce toxicity, and improve outcomes.
Journal ArticleDOI
Protease-sensitive regions in amyloid light chains: what a common pattern of fragmentation across organs suggests about aggregation
Giulia Mazzini,Stefano Ricagno,Serena Caminito,Paola Rognoni,Paolo Milani,Mario Nuvolone,Marco Basset,Andrea Foli,Rosaria Russo,Giampaolo Merlini,Giovanni Palladini,Francesca Lavatelli +11 more
TL;DR: This paper identified and compared the fragmentation sites of amyloid light chains (LCs) from multiple organs of an AL-55 patient, including kidney and subcutaneous fat, alongside those previously detected in heart of the same patient, were aligned and mapped on the LC's dimeric and fibrillar states.
Journal ArticleDOI
Machine learning analyses of antibody somatic mutations predict immunoglobulin light chain toxicity.
Maura Garofalo,Luca Piccoli,Margherita Romeo,Maria Monica Barzago,Sara Ravasio,Sara Ravasio,Mathilde Foglierini,Mathilde Foglierini,Milos Matkovic,Jacopo Sgrignani,Raoul De Gasparo,Marco Prunotto,Luca Varani,Luisa Diomede,Olivier Michielin,Olivier Michielin,Antonio Lanzavecchia,Andrea Cavalli,Andrea Cavalli +18 more
TL;DR: In this paper, a machine learning approach was proposed to predict light chain toxicity in systemic light chain amyloidosis (AL), based on the distribution of somatic mutations acquired during clonal selection.
References
More filters
Journal ArticleDOI
Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
Journal ArticleDOI
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Paul D. Adams,Paul D. Adams,Pavel V. Afonine,Gábor Bunkóczi,Vincent B. Chen,Ian W. Davis,Nathaniel Echols,Jeffrey J. Headd,Li-Wei Hung,Gary J. Kapral,Ralf W. Grosse-Kunstleve,Airlie J. McCoy,Nigel W. Moriarty,Robert D. Oeffner,Randy J. Read,David S. Richardson,Jane S. Richardson,Thomas C. Terwilliger,Peter H. Zwart +18 more
TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
Journal ArticleDOI
MolProbity: all-atom structure validation for macromolecular crystallography
Vincent B. Chen,W. Bryan Arendall,Jeffrey J. Headd,Daniel A. Keedy,R.M. Immormino,Gary J. Kapral,Laura Weston Murray,Jane S. Richardson,David S. Richardson +8 more
TL;DR: MolProbity structure validation will diagnose most local errors in macromolecular crystal structures and help to guide their correction.
Journal ArticleDOI
Inference of macromolecular assemblies from crystalline state.
E. Krissinel,Kim Henrick +1 more
TL;DR: A new method, based on chemical thermodynamics, is developed for automatic detection of macromolecular assemblies in the Protein Data Bank (PDB) entries that are the results of X-ray diffraction experiments, as found, biological units may be recovered at 80-90% success rate, which makesX-ray crystallography an important source of experimental data on macromolescular complexes and protein-protein interactions.
Journal ArticleDOI
MOLREP: an Automated Program for Molecular Replacement
Alexei A. Vagin,Alexei Teplyakov +1 more
TL;DR: MOLREP as mentioned in this paper is an automated program for molecular replacement which utilizes effective new approaches in data processing and rotational and translational searching, such as automatic choice of all parameters, scaling by Patterson origin peaks and soft resolution cut-off.