Structural differences between brain beta 1- and beta 2-tubulins: implications for microtubule assembly and colchicine binding.
Brain beta 1- and beta 2-tubulins are the major and minor beta-tubulin components of chordate brain tissue, respectively. Two cysteines of beta 1, but not beta 2, can be specifically cross-linked with the bifunctional sulfhydryl reagent N,N'-ethylenebis(iodoacetamide) (EBI). They are in positions 239 and 354. Although separated by 115 amino acid residues along the beta 1-chain, the two sulfur atoms are maximally 9 A apart in the beta 1 tertiary structure. The failure of beta 2 to form a similar cross-bridge is due to the absence of a cysteine in position 239. At least 10 other sequence differences are also present between beta 1 and beta 2. Positions 239 and 354 of beta 1 probably occupy a key part of the tubulin molecule. The microtubule assembly inhibitors colchicine and podophyllotoxin appear to bind on or near this site and EBI is a potent inhibitor of microtubule assembly. Furthermore, the beta 1-cysteine in position 239 appears to be the most reactive in brain tubulin under the given conditions. The marked difference between beta 1 and beta 2 in this critical region suggests that they may have different functions in brain tissue.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D003078:Colchicine / Q000378:metabolism*; D003432:Cross-Linking Reagents; D003545:Cysteine; D005029:Ethylenediamines; D008870:Microtubules / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*
D003432:Cross-Linking Reagents; D005029:Ethylenediamines; D014404:Tubulin; C032156:N,N'-ethylenebis(iodoacetamide); D003545:Cysteine; D003078:Colchicine