Solution structure of the spectrin repeat: A left-handed antiparallel triple-helical coiled-coil

被引:129
作者
Pascual, J [1 ]
Pfuhl, M [1 ]
Walther, D [1 ]
Saraste, M [1 ]
Nilges, M [1 ]
机构
[1] EUROPEAN MOL BIOL LAB, D-69012 HEIDELBERG, GERMANY
关键词
cell elasticity; membrane skeleton; hemolytic anemias; heteronuclear NMR;
D O I
10.1006/jmbi.1997.1344
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 H-1-chemical shifts. The final ensemble of 20 structures shows an average RMSD of 1.52 Angstrom 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. (C) 1997 Academic Press Limited.
引用
收藏
页码:740 / 751
页数:12
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