Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
Biochemistry. 2012 Jun 26;51(25):5041-51. doi: 10.1021/bi3002924. Epub 2012 Jun 14.
Type II polyproline helices (PPII) are a fundamental secondary structure of proteins, common in globular and nonglobular regions and important in cellular signaling. We developed a propensity scale for PPII using a host-guest system with sequence Ac-GPPXPPGY-NH(2), where X represents any amino acid. We found that proline has the highest PPII propensity, but most other amino acids display significant PPII propensities. The PPII propensity of leucine was the highest of all propensities of non-proline residues. Alanine and residues with linear side chains displayed the next highest PPII propensities. Three classes of residues displayed lower PPII propensities: β-branched amino acids (Thr, Val, and Ile), short amino acids with polar side chains (Asn, protonated Asp, Ser, Thr, and Cys), and aromatic amino acids (Phe, Tyr, and Trp). tert-Leucine particularly disfavored PPII. The basis of the low PPII propensities of aromatic amino acids in this context was significant cis-trans isomerism, with proline-rich peptides containing aromatic residues exhibiting 45-60% cis amide bonds, due to Pro-cis-Pro-aromatic and aromatic-cis-Pro amide bonds.
II 型聚脯氨酸螺旋（PPII）是蛋白质的基本二级结构，常见于球状和非球状区域，在细胞信号转导中具有重要作用。我们使用 Ac-GPPXPPGY-NH2 序列的主体 - 客体系统开发了一种 PPII 倾向尺度，其中 X 代表任何氨基酸。我们发现脯氨酸具有最高的 PPII 倾向，但大多数其他氨基酸也显示出显著的 PPII 倾向。亮氨酸的 PPII 倾向是所有非脯氨酸残基中最高的。丙氨酸和具有线性侧链的残基显示出下一个最高的 PPII 倾向。三类残基显示出较低的 PPII 倾向：β-支链氨基酸（Thr、Val 和 Ile）、带极性侧链的短氨基酸（Asn、质子化的 Asp、Ser、Thr 和 Cys）和芳香族氨基酸（Phe、Tyr 和 Trp）。叔亮氨酸特别不利于 PPII。在这种情况下，芳香族氨基酸的 PPII 倾向较低的原因是显著的顺反异构，含有芳香族残基的脯氨酸丰富肽含有 45-60%的顺酰胺键，这是由于 Pro-cis-Pro-芳香族和芳香族-cis-Pro 酰胺键所致。
