| Literature References | 1. CLEVELAND, D.W. AND SULLIVAN, K.F.
Molecular biology and genetics of tubulin.
ANNU.REV.BIOCHEMISTRY 54 331-365 (1985).
2. JOSHI, H.C. AND CLEVELAND, D.W.
Diversity among tubulin subunits: toward what functional end?
CELL MOTIL.CYTOSKELETON 16 159-163 (1990).
3. MITCHISON, T.J.
Localization of an exchangeable GTP binding site at the plus end of
microtubules.
SCIENCE 261 1044-1047 (1993).
4. HESSE, J., THIERAUF, M. AND PONSTINGL, H.
Tubulin sequence region beta 155-174 is involved in binding exchangeable
guanosine triphosphate.
J.BIOL.CHEM. 262 15472-15475 (1987).
5. JOSHI, H.C.
Gamma-tubulin: the hub of cellular microtubule assemblies.
BIOESSAYS 15 637-643 (1993).
6. BAUMANN, M.H., WISNIEWSKI, T., LEVY, E., PLANT, G.T. AND GHISO, J.
C-terminal fragments of alpha- and beta-tubulin form amyloid fibrils in
vitro and associate with amyloid deposits of familial cerebral amyloid
angiopathy, British type.
BIOCHEM.BIOPHYS.RES.COMMUN. 219 238-242 (1996).
7. LEWIS, S.A., GILMARTIN, M.E., HALL, J.L. AND COWAN, N.J.
Three expressed sequences within the human beta-tubulin multigene family
each define a distinct isotype.
J.MOL.BIOL. 182 11-20 (1985).
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| Documentation | Microtubules are polymers of tubulin, a dimer of two 55kDa subunits,
designated alpha and beta [1,2]. Within the microtubule lattice, alpha-beta
heterodimers associate in a head-to-tail fashion, giving rise to microtubule
polarity. Fluorescent labelling studies have suggested that tubulin is
oriented in microtubules with beta-tubulin toward the plus end [3].
For maximal rate and extent of polymerisation into microtubules, tubulin
requires GTP. Two molecules of GTP are bound at different sites, termed N
and E. At the E (Exchangeable) site, GTP is hydrolysed during incorporation
into the microtubule. Close to the E site is an invariant region rich in
glycine residues, which is found in both chains and is thought to control
access of the nucleotide to its binding site [4].
Most species, excepting simple eukaryotes, express a variety of closely-
related alpha- and beta-isotypes. A third family member, gamma-tubulin, has
also been identified in a number of species [5].
British type familial amyloidosis is an autosomal dominant disease
characterised by progressive dementia, spastic paralysis and ataxia [6].
Amyloid deposits from the brain tissue of an individual who died with this
disease have been characterised. Trypsin digestion and subsequent N-terminal
sequence analysis yielded a number of short sequences, all of which are
tryptic fragments of the C-termini of human alpha- and beta-tubulin [6].
Consistent with the definition of amyloid, synthetic peptides based on the
sequences of these fragments formed fibrils in vitro, suggesting that the
C-termini of both alpha- and beta-tubulin are closely associated with the
amyloid deposits of this type of amyloidosis [6].
The amino acid sequences encoded by beta-tubulin genes have revealed a high
level of overall similarity, but significant divergence between their
C-termini [7]. The pattern of expression of the beta-tubulin genes has been
studied in several different human cell lines and has revealed varying
levels of and differential expression in different cell lines [7]. It
appears that distinct human beta-tubulin isotypes are encoded by genes
whose exon size and number has been conserved evolutionarily, but whose
pattern of expression may be regulated either co-ordinately or uniquely [7].
BETATUBULIN is a 13-element fingerprint that provides a signature for beta
tubulins. The fingerprint was derived from an initial alignment of 34
sequences. The motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise the
beta-tubulins but distinguish them from the rest of the tubulin family.
Three iterations on SPTR37_10f were required to reach convergence, at which
point a true set comprising 175 sequences was identified. Several partial
matches were also found, all of which are beta-tubulins that fail to make
significant matches with one or more motifs.
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