Figure 3.

Pathogenic Lm mutations are located in the areas of high sequence conservation. Lm isoforms share significant sequence identity (Supplementary Table 1). We used Clustal Omega⁶⁰ for sequence alignment of the following Lm isoforms implicated in Lm disorders: (a) α1 (Homo sapiens and Mus musculus LAMA1; the mouse Lm α1 was used for cryo-EM structure determination¹³), α2 (LAMA2), α5 (LAMA5), and (b) β1 (LAMB1), β2 (LAMB2), and β3 (LAMB3). Class 1, 2, 3 and 4 mutations are conserved among different Lm variants and are indicated by orange, purple, cyan and gray letters, respectively. Secondary structure elements are indicated above amino acid sequences (α-helices as bars and β-strands as arrows in green and red for Lm α and β variants, respectively). Some of the conserved protein regions involved in formation of inter-subunit interfaces and hydrophobic cores are indicated above the amino acid sequences as orange and gray bars, respectively.