Cytoskeletal proteins belonging to the spectrin family have an elongated 
structure composed of repetitive units. The three-dimensional solution structure 
of the 16th repeat from chicken brain alpha-spectrin (R16) has been determined 
by NMR spectroscopy and distance geometry-simulated annealing calculations. We 
used a total of 1035 distance restraints, which included 719 NOE-based values 
obtained by applying the ambiguous restraints for iterative assignment (ARIA) 
method. In addition, we performed a direct refinement against 1H-chemical 
shifts. The final ensemble of 20 structures shows an average RMSD of 1.52 A from 
the mean for the backbone atoms, excluding loops and N and C termini. R16 is 
made up of three antiparallel alpha-helices separated by two loops, and folds 
into a left-handed coiled-coil. The basic unit of spectrin is an antiparallel 
heterodimer composed of two homologous chains, beta and alpha. These assemble a 
tetramer via a mechanism that relies on the completion of a single repeat by 
association of the partial repeats located at the C terminus of the beta-chain 
(two helices) and at the N terminus of the alpha-chain (one helix). This 
tetramer is the assemblage able to cross-link actin filaments. Model building by 
homology of the "tetramerization" repeat from human erythrocyte spectrin 
illuminates the possible role of point mutations which cause hemolytic anemias.