The structure of the ankyrin-binding site of β-spectrin reveals how tandem spectrin-repeats generate unique ligand-binding properties

Spectrin and ankyrin participate in membrane organization, stability, signal transduction, and protein targeting; their interaction is critical for erythrocyte stability. Repeats 14 and 15 of βI-spectrin are crucial for ankyrin recognition, yet the way spectrin binds ankyrin while preserving its repeat structure is unknown. We have solved the crystal structure of the βI-spectrin 14,15 di-repeat unit to 2.1 Å resolution and found 14 residues critical for ankyrin binding that map to the end of the helix C of repeat 14, the linker region, and the B-C loop of repeat 15. The tilt (64°) across the 14,15 linker is greater than in any published di-repeat structure, suggesting that the relative positioning of the two repeats is important for ankyrin binding. We propose that a lack of structural constraints on linker and inter-helix loops allows proteins containing spectrin-like di-repeats to evolve diverse but specific ligand-recognition sites without compromising the structure of the repeat unit. The linker regions between repeats are thus critical determinants of both spectrin's flexibility and polyfunctionality. The putative coupling of flexibility and ligand binding suggests a mechanism by which spectrin might participate in mechanosensory regulation.

Efficiency of antioxidant therapy in patients with acute myocardial infarction and unstable stenocardia

The efficiency of preductal (trimetazidin), essentiale, li postabil and vitamin E in acute myocardial infarction and unstable stenocardia is estimated. It is shown that in unstable stenocardia and in the acute period of myocardial infarction the high level of lipid peroxide oxidation and the decrease of erythrocyte stability are observed. The clinical efficiency of antioxidants in the treatment of the acute forms of ischemic heart disease is proved: the antianginal effect is achieved, readaptation possibilities of patients to physical loads are increased, effect of anti rhythmical drugs is intensified, myocardial infarction size is limited (especially in using preductal). The presence of pronounced antioxidant and membranoprotective properties in preductal, lipostabil, essentiale comparing well with -tokopherol is proved. It is shown that preductal manifests the antianginal effect by the microcirculation system and metabolism correction. Antioxidants promote the decrease of blood elements sledge and increase of the number of perfused capillars.