Hydrophobic basis of packing in globular proteins.
Hydrophobic basis of packing in globular proteins.
复制标题
球状蛋白质堆积的疏水基础。
DOI：
10.1073/pnas.77.8.4643
复制
发表时间：
1980
影响因子：
11.1
通讯作者：
Roy,S
中科院分区：
文献类型：
--
作者：
Rose,GD;Roy,S
球状蛋白质的自组装通常被描述为成核过程，其中二级结构片段中的氢键是进一步折叠的先决条件。我们在这里表明，这一概念是不可能的，因为隐藏的内部区域和折叠蛋白质的肽链转角（即，内部和外部）仅由沿着链的沿着顺序的残基的疏水性预测。螺旋和链跨越蛋白质，并且观察到的二级结构与仅从疏水性考虑预测被掩埋的区域一致。我们的证据表明，富含疏水残基的线性链区域作为相互折叠的小簇，伴随着或甚至稍后固定二级结构。在这个折叠过程中，螺旋或链将作为给定簇的几个能量上有利的替代物之一出现，然后在簇缔合时二级结构构象之间的平衡发生变化。线性链疏水性在局部最大值和最小值之间交替，并且这些极值将多肽链划分成结构片段。这种分配在X射线结构中被视为在肽链转角之间括号内的同向片段，其中片段最常表达为螺旋和链。链段相互作用定义了分子内部的几何形状，链转角描述了分子海岸线的主要特征。线性链疏水性的分子的分割对可能的折叠事件施加了主要的几何约束。
The self-assembly of globular proteins is often portrayed as a nucleation process in which the hydrogen bonding in segments of secondary structure is the precondition for further folding. We show here that this concept is unlikely because both the buried interior regions and the peptide chain turns of the folded protein (i.e., inside and outside) are predicted solely by the hydrophobicity of the residues, taken in sequential order along the chain. The helices and strands span the protein, and this observed secondary structure is seen to coincide with the regions predicted to be buried from hydrophobicity considerations alone. Our evidence suggests that linear chain regions rich in hydrophobic residues serve as small clusters that fold against each other, with concomitant or even later fixation of secondary structure. A helix or strand would arise in this folding process as one of a few energetically favorable alternatives for a given cluster, followed by a shift in the equilibrium between secondary structure conformers upon cluster association. the linera chain hydrophobicity alternates between locally maximal and minimal values, and these extrema partition the polypeptide chain into structural segments. This partitioning is seen in the x-ray structure as isodirectional segments bracketed between peptide chain-turns, with the segments expressed most often as helices and strands. the segment interactions define the geometry of the molecular interior and the chain-turns describe the predominant features of the molecular coastline. The segmentation of the molecule by linear chain hydrophobicity imposes a major geometric constraint upon possible folding events.