TI  - <prot>Spectrin cagliari</prot>. an Ala--&gt;Gly substitution in helix 1 of <prot>beta spectrin</prot>
      repeat 17 that severely disrupts the structure and self-association of the
      erythrocyte spectrin heterodimer.
PG  - 22656-62
AB  - The spectrin tetramer, the principal structural element of the red cell
      membrane skeleton, is formed by stable head-to-head self-association of
      two   spectrin   heterodimers. The self-association site appears to be formed
      by interactions between helices 1 and 2 of  <prot>beta spectrin</prot>  repeat 17 of one
      dimer with helix 3 of  <prot>alpha spectrin</prot>  repeat 1 of the other dimer to form
      two combined alpha-beta triple-helical segments. The head of the
      heterodimer appears to involve similar intradimer interactions. We
      describe the first example of an amino acid substitution in helix 1 of
      this combined alpha-beta triple-helical segment, which, although
      relatively minor, profoundly impairs tetramer formation. Strikingly, low
      angle rotary shadowing electron microscopy of isolated spectrin dimers
      reveals that this mutation also severely disrupts the head of the
      heterodimer causing it to be open. Following linkage studies which were
      most consistent with a <prot>beta spectrin</prot> gene mutation, a nucleotide change
      was identified in codon 2018, resulting in an Ala--&gt;Gly substitution in
      the first helical domain of <prot>beta spectrin</prot> repeat 17. Because glycine is a
      strong helix breaker, this change is predicted to disrupt the conformation
      of this helical domain. Our results indicate that this helical domain must
      play direct roles in the alpha-beta interdimer interactions that form the
      self-association site of the tetramer and in the alpha-beta intradimer
      interactions at the head of the heterodimer.
AD  - Department of Biomedical Research, St. Elizabeth's Hospital of Boston,
