Domain organization and sequence alignment of malin and TRIM32. A) Malin shares sequence features with TRIM32. Human sequences were aligned using MAFFT and displayed in MacVector. Predicted secondary structure is displayed over the sequences with ovals representing α-helices and arrows representing β-sheets. Grey structural elements are shared by malin and TRIM32, black domains are specific to TRIM32, and tan domains are specific to malin. The RING domain is highlighted in light red and the NHL domains are highlighted in light green. Malin-specific Lafora disease missense mutations are highlighted in blue and when conserved the similar amino acid in TRIM32 is highlighted in blue. The position of D233 in malin and D487 in TRIM32 is highlighted in red. B) Alignment of malin and TRIM32 structural models. NHL-containing fragments of both sequences (amino acids 113-396 in malin; 358-646 in TRIM32) were submitted to the ESypred3D server and modeled using structure of M. tuberculosis PknD (PDB:1rwl) as a template. Both structural models (green for malin, red for TRIM32) were displayed and aligned using PyMOL, showing a repetition of six NHL domains in both cases. C) Mapping of mutations found in patients in structural models of malin. Amino acids reported to cause disease are shown in blue. D) Mapping of Limb-Girdle muscular dystrophy mutations in TRIM32. The position of D487N is highlighted and is structurally analogous to malin-D233A Lafora disease mutation.
Romá-Mateo et al. BMC Evolutionary Biology 2011 11:225 doi:10.1186/1471-2148-11-225