Figure 4
From: A human β-III-spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding
Leucine 253 side-chain hydrophobic interactions bridge the CH1-CH2 domain interface.
(A) β-III-spectrin CH1 domain alpha-helix A and CH2 domain alpha-helices E, F and G (green) are shown aligned with β-II-spectrin CH2 domain crystal structure alpha-helices E,F and G (grey). The side chain of β-III-spectrin leucine 253 (magenta) or β-II-spectrin leucine 250 (cyan) is oriented towards CH1 domain alpha-helix A The β-III-spectrin leucine 253 side-chain is predicted to form hydrophobic interactions with threonine 62, lysine 65 and tryptophan 66 of CH1 domain alpha-helix A and with threonine 271, tyrosine 272 and threonine 275 of CH2 domain alpha-helix G. (B) ClustalW alignment showing that human (Homo sapiens, Hs) β-III-spectrin leucine 253 and its predicted hydrophobic contacts are conserved in human β-II-spectrin, mouse (Mus musculus, Mm) β-III-spectrin, fly (Drosophila melanogaster, Dm) β-spectrin and in the homologous ABD of human dystrophin. (C) The dystrophin residue equivalent of β-III-spectrin leucine 253, leucine 212 (magenta), is inserted into a nearly identical hydrophobic pocket at the CH domain interface in the crystal structure of the dystrophin amino-terminal ABD (PDB ID: 1DXX), a template structure used in generation of the β-III-spectrin homology model.
