Fig. 2: Cryo-EM structure of cardiac fibrils from ATTRv-I84S patient 2.

a Stitching of the 2D classes of curvy fibrils with the absent gate fold, showing the β-strand separation and the full twist of the fibril. b 3D class averages of curvy fibrils showing the closed gate fold (left) and the absent gate fold (right). c–e Structure and density maps of the absent gate fold. c Cryo-EM model of the absent gate fold showing the crossover distance. d Cryo-EM density map and atomic model of the absent gate fold. The model contains two fragments of transthyretin colored pink (residues Leu 12 to Lys 35) and light sea green (Ile 68 to Asn 124). The mutation site is colored black. e Local resolution map of the absent gate fold, where blue indicates higher resolution and red indicates lower resolution. f Structural alignment of the closed gate fold of patient 1 (purple) and the absent gate fold of patient 2 (red) with an overall r.m.s.d. of 2.1 Å. The differences in the tilt of each layer (bottom panel) and the divergence of the two fragments observed in the absent gate fold (with distances of 3.6 Å in the N-terminus and 2.4 Å in the C-terminus) contribute to this r.m.s.d.