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Supplementary Data Figures

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Supplementary Data Figure 1 | Sequence alignment of Piezo homologous.

Based on topology prediction and structurally resolved information, secondary structural elements of

mPiezo1 are indicated above the sequence alignment and color-coded for helices within different

THUs. Disease related mutations are indicated by triangles and pentacles below the sequences and

colored according to different diseases (red triangle for recessive generalized lymphatic dysplasia in

human Piezo1, yellow triangle for dominant dehydrated stomatocytosis/hereditary xerocytosis in

human Piezo1, green triangle for colorectal adenomatous polyposis in human Piezo1, blue pentacle

for scoliosis with peripheral sensory dysfunction in human Piezo2, purple pentacles for dominant

distal arthrogryposes type 3, type 5 (DA5), and Marden-Walker syndrome).

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Supplementary Data Figure 2 | Uncropped WB images related to Extended Data Figure 8c, d

and 9b

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Supplementary Table 1 EM data collection, data processing and model refinement.