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Table 1 Description and results of the biochemical characterization of 16 new nemaline myopathy causing α-skeletal muscle actin mutants.

From: Phenotypes induced by NM causing α-skeletal muscle actin mutants in fibroblasts, Sol 8 myoblasts and myotubes

Mutant phenotype Folding CAP ABP copol In actin structure (Kabsch) reference
WT   + + + ++   
D25N severe NEM ┼ + + + ++ Subdomain I, Close to ATP cleft [4]
V35L severe NEM + + + ++ Subdomain II, Buried [19]
P38L severe NEM + + + + Subdomain II [19]
H73L severe NEM ┼ + - +, VDBP+/- + Subdomain II, In ATP cleft, stabilizing interaction with D179 [19]
I75L severe NEM + + +, VDBP+/- ++ Subdomain II, In ATP cleft [19]
E83K Typical NEM +/- + + + more aggr Helix [19]
R116H Severe NEM ┼ + +/- + + + more aggr Subdomain I, Helix, close to ATP cleft [4]
V163M IRM +/- + + + more aggr Subdomain III, Buried, near ATP-cleft [27]
Q246R mild, typical and severe + + + ++ Subdomain IV, Close to F-actin contact [19, 20]
G251D severe NEM + +/- + ++ Subdomain IV, At surface [19]
R256H severe NEM + - + + Subdomain IV, Close to F-actin contact [2]
M269R mild NEM + + + + Subdomain IV, F-actin contact, hydrophobic plug [21]
  1. The properties investigated here are folding, binding to cyclase associated protein (CAP), binding to the actin binding proteins (ABP) thymosinβ4, DNAseI and Vitamin D binding protein (VDBP) and copolymerisation with rabbit α-skeletal muscle actin (copol). Also the location in the actin structure according to Kabsch et al. [18] is indicated, in addition to the patients phenotype as presented in the reference with NEM = nemaline myopathy, sarcoplasmic nemaline bodies; IRM = intranuclear rod myopathy.