IS THE HYDROPHOBIC EFFECT STABILIZING OR DESTABILIZING IN PROTEINS - THE CONTRIBUTION OF DISULFIDE BONDS TO PROTEIN STABILITY
IS THE HYDROPHOBIC EFFECT STABILIZING OR DESTABILIZING IN PROTEINS - THE CONTRIBUTION OF DISULFIDE BONDS TO PROTEIN STABILITY
复制标题
DOI：
10.1016/0022-2836(91)90551-g
复制
发表时间：
1991-01-20
影响因子：
5.6
通讯作者：
WILLIAMS, DH
中科院分区：
文献类型：
--
作者：
DOIG, AJ;WILLIAMS, DH
最近得出的结论是，疏水效应迄今为止被认为是蛋白质折叠的主要驱动力，它使折叠状态相对于未折叠状态不稳定。我们总结了从溶剂转移实验中获得的疏水效应的特性，并表明最近的结论是由二硫键、金属或辅因子引起的未折叠状态下交联的伪影。我们表明，对于数据集中的蛋白质，交联令人惊讶地破坏了折叠结构的熵稳定性，但在更大程度上稳定了它们的焓。我们还计算了这些未折叠蛋白质的非极性表面积。这些表面积因交联而减少。缺乏约束的蛋白质（例如肌红蛋白）的展开状态可以通过包含 α 螺旋和 β 片层二面角的残基混合物很好地近似。未折叠蛋白质的表面积不能通过对各个残基的表面积求和来获得，因为这忽略了任何不可避免的侧链-侧链相互作用。
It has been recently concluded that the hydrophobic effect, hitherto regarded as a major driving force in the folding of proteins, destabilizes the folded state relative to the unfolded state. We summarize the properties of the hydrophobic effect obtained from solvent transfer experiments and show that the recent conclusion is an artifact of crosslinking in the unfolded state, caused by disulphide bonds, metals or cofactors. We show that, for the proteins in the data set, crosslinks surprisingly destabilize folded structures entropically, but stabilize them enthalpically to a greater extent. We also calculate non-polar surface areas of these unfolded proteins. These surface areas are decreased by crosslinks. The unfolded state of proteins lacking constraints, such as myoglobin, is well approximated by a mixture of residues containing α-helical and β-sheet dihedral angles. Surface areas of unfolded proteins cannot be obtained by summing the surface areas of individual residues, since this ignores any unavoidable side-chain-side-chain interactions.