Extended Data Table 1:

Cryo-EM data collection, refinement and validation statistics

	V337M case3			R406W case2		in vitro
Data collection
Microscope	Titan Krios			Titan Krios		Titan Krios
Voltage (kV)	300			300		300
Detector	Falcon4			Falcon4		Falcon4i
Magnification	96,000			96,000
Electron exposure (e-/Å2)	40			40		40
Defocus range (μm)	−1.0 to −2.0			−1.0 to −2.0		−1.0 to −2.0
Pixel size (Å)	0.824			0.824		0.727
Data processing	PHF	SF	TF	PHF	CTE Type I	PHF
Box size (pixel)	400	400	400	400	400	384
Symmetry imposed	C1	C1	C3	C1	C1	C1
Initial particle images (no)	510,657			144,450		124,071
Final particle images (no)	330,371	75,617	104,579	134,218	10,232	37,720
Map resolution (Å) FSC threshold 0.143	2.8	3.3	2.3	3.0	5.0	2.8
Helical rise (Å)	2.37	4.76	4.76	2.37	2.37	2.37
Helical twist (°)	179.4	−1.07	−0.88	179.4	179.4	179.2
Refinement
Model resolution (Å) FSC threshold 0.5	2.9	3.5	2.5	3.2	5.0	2.9
Map sharpening B factor (Å2)	−56	−83	−43	−70		−42
Model composition
Non-hydrogen atoms	4116	4704	3528	3522		3414
Protein residues	539	616	462	462		444
Ligands	0	0	0	0		0
B factors (A2)
Protein	208.8	276.3	200.3	237.2		180.2
R.m.s. deviations
Bond lengths (Å)	0.0063	0.0063	0.0063	0.0069		0.0067
Bond angles (°)	1.390	1.347	1.393	1.485		1.305
Validation
MolProbity score	1.93	2.37	2.28	2.18		1.75
Clashscore	6.58	5.86	5.58	4.89		4.31
Poor rotamers (%)	1.49	5.97	4.48	4.48		0
Ramachandran plot
Favored (%)	93.33	92.67	92.00	93.33		90.28
Allowed (%)	6.67	7.33	8.00	6.67		9.72
Disallowed (%)	0	0	0	0		0
EMDB	EMD-19846	EMD-19849	EMD-19852	EMD-19854		EMD-19855
PDB	9EO7	9EO9	9EOE	9EOG		9EOH