Deville Julie, Rey Julien, Chabbert Marie
CNRS UMR 6214-INSERM U771, Université d'Angers, Faculté de Médecine, 3 rue Haute de Reculée, 49045 Angers, France.
Proteins. 2008 Jul;72(1):115-35. doi: 10.1002/prot.21879.
Alpha-helices are the most common secondary structures found in globular proteins. In this report, we analyze the stereochemical and sequence properties of helix-X-helix (HXH) motifs in which two alpha-helices are linked by a single residue, in search of characteristic structures and sequence signals. The analysis is carried out on a database of 837 nonredundant HXH motifs. The kinks are characterized by the bend angle between the axes of the N-terminal and C-terminal helices and the wobble angle corresponding to the rotation of C-terminal helix axis on the plane perpendicular to the N-terminal one. The phi-psi dihedral angles of the linker residue are clustered in six distinct areas of the Ramachandran plot: two areas are located in the additional allowed alpha region (alpha(1) and alpha(2)), two areas are in the additional allowed beta region (beta(1) and beta(2)) and two areas have positive phi values (alpha(L) and beta(M)). Each phi/psi region corresponds to characteristic bend and wobble angles and amino acid distributions. Bend angles can vary from 0 degrees to 160 degrees. Most wobble angles correspond to a counter-clockwise rotation of the C-terminal helix. Proline residues are rigorously excluded from the linker position X but have a high propensity at position X+1 of the beta(1) and beta(2) motifs (12 and 7, respectively) and at position X+3 of the alpha(1) motifs (9). Glycine linkers are located either in the alpha(L) region (20%) or in the beta(M) region (80%). This latter conformation is characterized by a marked bend angle (124 degrees +/- 18 degrees) and a clockwise wobble. Among other amino acids, Asn is remarkable for its high propensity (>3) at the linker position of the alpha(2), beta(1), and beta(2) motifs. Stabilization of HXH motifs by H-bonds between polar side chains of the linker and polar groups of the backbone is determined. A method based on position-specific scoring matrices is developed for conformational prediction. The accuracy of the predictions reaches 80% when the method is applied to proline-induced kinks or to kinks with bend angles in the 50 degrees-100 degrees range.
α-螺旋是球状蛋白质中最常见的二级结构。在本报告中，我们分析了螺旋-X-螺旋（HXH）基序的立体化学和序列特性，其中两个α-螺旋由单个残基连接，以寻找特征结构和序列信号。分析是在一个包含837个非冗余HXH基序的数据库上进行的。扭结的特征在于N端和C端螺旋轴之间的弯曲角度以及对应于C端螺旋轴在垂直于N端螺旋轴的平面上旋转的摆动角度。连接残基的φ-ψ二面角聚集在拉氏图的六个不同区域：两个区域位于额外允许的α区域（α(1)和α(2)），两个区域位于额外允许的β区域（β(1)和β(2)），两个区域具有正的φ值（α(L)和β(M)）。每个φ/ψ区域对应于特征性的弯曲和摆动角度以及氨基酸分布。弯曲角度可从0度变化到160度。大多数摆动角度对应于C端螺旋的逆时针旋转。脯氨酸残基被严格排除在连接位置X之外，但在β(1)和β(2)基序的X+1位置（分别为12个和7个）以及α(1)基序的X+3位置（9个）具有较高的倾向性。甘氨酸连接子位于α(L)区域（20%）或β(M)区域（80%）。后一种构象的特征是具有明显的弯曲角度（124度±18度）和顺时针摆动。在其他氨基酸中，天冬酰胺在α(2)、β(1)和β(2)基序的连接位置具有较高的倾向性（>3）。确定了连接子的极性侧链与主链的极性基团之间通过氢键对HXH基序的稳定作用。开发了一种基于位置特异性评分矩阵的构象预测方法。当该方法应用于脯氨酸诱导的扭结或弯曲角度在50度至100度范围内的扭结时，预测准确率达到80%。
