Cell Motil Cytoskeleton 2001 Aug 01;494:229-40. doi: 10.1002/cm.1036.

Light chains of mammalian cytoplasmic dynein: identification and characterization of a family of LC8 light chains.

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Cytoplasmic dynein is a large multisubunit motor protein that moves various cargoes toward the minus ends of microtubules. In addition to the previously identified heavy, intermediate, and light intermediate chains, it has recently been recognized that cytoplasmic dynein also has several light chain subunits with apparent molecular weights between 8-20 kDa. To systematically identify the light chains of purified rat brain cytoplasmic dynein, peptide sequences were obtained from each light chain band resolved by gel electrophoresis. Both members of the tctex1 light chain family, tctex1 and rp3, were identified in a single band. Only one member of the roadblock family, roadblock-2, was found. Two members of the LC8 family were resolved as separate bands, the previously identified LC8 subunit, and a second novel cytoplasmic dynein family member, LC8b. The tissue distribution of these two dynein LC8 subunits differed, although LC8b was the major family member in brain. Database searches found that both LC8a and LC8b were also present in several mammalian species, and a third mammalian LC8 sequence, LC8c was found in the human database. The amino acid sequences of both LC8a and LC8b were completely conserved in mammals. LC8a and LC8b differ in only six of the 89 amino acids. The amino acid differences between LC8a and LC8b were located near the N-terminus of the molecules, and most were in the outward facing alpha-helices of the LC8 dimer. When the mammalian LC8a sequence was compared to the LC8 sequences found in six other animal species including Xenopus and Drosophila, there was, on average, 94% sequence identity. More variation was found in LC8 sequences obtained from plants, fungi, and parasites. LC8c differed from the other two human LC8 sequences in that it has amino acid substitutions in the intermediate chain binding domain at the C-terminal of the molecule. The position of amino acid substitutions of the three mammalian LC8 family members is consistent with the hypothesis that they bind to different proteins.

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Species referenced: Xenopus
Genes referenced: dnai1 dync1li1 dynll1 dynll2 mapre3