Structural differences between brain beta 1- and beta 2-tubulins: implications for microtubule assembly and colchicine binding.

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Abstract
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.