RT Journal Article SR Electronic T1 Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain (AL) amyloidosis patient JF bioRxiv FD Cold Spring Harbor Laboratory SP 444901 DO 10.1101/444901 A1 Paolo Swuec A1 Francesca Lavatelli A1 Masayoshi Tasaki A1 Cristina Paissoni A1 Paola Rognoni A1 Martina Maritan A1 Francesca Brambilla A1 Paolo Milani A1 Pierluigi Mauri A1 Carlo Camilloni A1 Giovanni Palladini A1 Giampaolo Merlini A1 Stefano Ricagno A1 Martino Bolognesi YR 2018 UL http://biorxiv.org/content/early/2018/10/17/444901.abstract AB Systemic light chain (AL) amyloidosis is a life-threatening disease caused by aggregation and deposition of monoclonal immunoglobulin light chains (LC) in target organs. Severity of heart involvement is the most important factor determining prognosis. Here, we report the 4.0 Å resolution cryo-electron microscopy (cryo-EM) map and structural model of amyloid fibrils extracted from the heart of an AL patient affected by severe amyloid cardiomyopathy. The fibrils are composed of one asymmetric protofilament, showing typical 4.9 Å stacking and parallel cross-β architecture. Two distinct polypeptide stretches belonging to the LC variable domain (Vl) could be modelled in the density (total of 77 residues), stressing the role of the Vl domain in fibril assembly and LC aggregation. Despite high levels of Vl sequence variability, residues stabilising the observed fibril core are conserved through several Vl domains, highlighting structural motifs that may be common to misfolded LCs. Our data shed first light on the architecture of life-threatening LC amyloid deposits, and provide a rationale for correlating LC amino acid sequences and fibril structures.