Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy
J. Clin. Invest. Joachim Schessl, et al. 118:904 doi:10.1172/JCI34450 [Go to this article.]

Figure 3
Mutations in FHL1 identified in patients with RBM affect conserved cysteine and histidine residues within the second LIM domain. (A) Pedigrees of the 4 families with affected members, indicating mutations in FHL1. Closed symbols designate affected individuals. (B) Schematic representation of the domain structure of FHL1 consisting of 4 LIM domains (LIM1–4) with an additional N-terminal half-LIM domain (Z). All 4 mutations are located in the second LIM domain and affect residues (boxed in red) that are absolutely conserved in orthologs from species down to mosquitoes. (C) Location of the mutations (highlighted in red) within the consensus sequence of the LIM domain and its 8 zinc coordinating residues. X denotes any amino acid. (D) Topology of zinc coordination. Green circles indicate zinc-binding residues. Arrows point to mutated residues. (E) Mutated residues (highlighted in red) superimposed on the NMR structure of the second LIM domain of FHL1 (RIKEN; http://www.genome.jp/dbget-bin/www_bget?pdb+1X63). Zinc atoms are indicated as gray spheres. Note that C153 falls into the α-helical domain at the C-terminal end of the LIM domain.