C-capping and helix stability: the Pro C-capping motif.
C-capping and helix stability: the Pro C-capping motif.
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DOI：
10.1006/jmbi.1997.1322
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发表时间：
1997-11
影响因子：
5.6
通讯作者：
J. Prieto;L. Serrano
中科院分区：
文献类型：
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作者：
J. Prieto;L. Serrano
在这里，我们已经进行了蛋白质数据库的统计分析，以找到新的推定的本地C-末端基序的α-螺旋。我们的分析表明，某些组合的X-Pro对（Asn，Cys，His，Phe，Tyr，Trp，Ile，瓦尔和Leu），其中残基X是C-帽和Pro在位置C '，比预期的更丰富。在那些对中，除了脂肪族残基之外，C'处Pro残基的存在倾向于将C-帽位置处残基的phi和psi二面角分别限制在约-130度、70度。对于芳族残基以及His，chi 1角约为-60度，并且His和芳族环的边缘靠近残基i - 4的羰基。在残基C-帽具有上述二面角的所有对中，C'处Pro的主链氨基接近α-螺旋的最后三个主链羰基。上述结构排列表明在位置C-帽和C'处的残基与螺旋大偶极子存在稳定静电相互作用。我们将这种假定的局部基序命名为前加帽基序。为了评估其在螺旋稳定性中的重要性，我们通过核磁共振（NMR）和远紫外圆二色性（CD）分析了一组基于聚丙氨酸的肽，其含有上述对中的两个：His-Pro和Phe-Pro，以及相应的对照。就His-Pro对而言，我们发现了在水溶液中形成Pro封端基序的NMR证据。CD分析表明，Pro残基的存在改变了前面氨基酸的C-帽特性，在His和Phe的情况下使它们更有利。具有适当序列的Pro-加帽基序决定α-螺旋的C末端的位置并稳定具有Pro作为C'残基的螺旋构象。
Here we have performed a statistical analysis of the protein database to find new putative local C-terminal motifs in alpha-helices. Our analysis shows that certain combinations of X-Pro pairs (Asn, Cys, His, Phe, Tyr, Trp, Ile, Val and Leu), in which residue X is the C-cap and the Pro is at position C', are more abundant than expected. In those pairs, except for the aliphatic residues, the presence of the Pro residue at C' tends to restrict the phi and psi dihedral angles of the residue at position C-cap, around -130 degrees , 70 degrees , respectively. For the aromatic residues as well as for His, the chi1 angle is around -60 degrees and the edge of the His and aromatic rings are close to the carbonyl group of the residue i - 4. In all the pairs having the above dihedral angles for residue C-cap, the main-chain amino group of Pro at C' is close to the last three main-chain carbonyls of the alpha-helix. The above structural arrangements suggests the existence of a stabilising electrostatic interaction of the residues at positions C-cap and C' with the helix macrodipole. We have denominated this putative local motif, the Pro-capping motif. To asses its importance in helix stability we have analysed by nuclear magnetic resonance (NMR) and far-UV circular dichroism (CD) a set of polyalanine-based peptides containing two of the above pairs: His-Pro and Phe-Pro, as well as the corresponding controls. In the case of the His-Pro pair we have found NMR evidence for the formation of the Pro-capping motif in aqueous solution. CD analysis shows that the presence of a Pro residue alters the C-cap properties of the preceding amino acids in the case of His and Phe makes them more favourable. The Pro-capping motif with the appropriate sequence, determines the location of the C terminus of alpha-helices and stabilises the helical conformation having Pro as the C' residue.