Munson M, Balasubramanian S, Fleming K G, Nagi A D, O'Brien R, Sturtevant J M, Regan L
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
Protein Sci. 1996 Aug;5(8):1584-93. doi: 10.1002/pro.5560050813.
Here we describe how the systematic redesign of a protein's hydrophobic core alters its structure and stability. We have repacked the hydrophobic core of the four-helix-bundle protein, Rop, with altered packing patterns and various side chain shapes and sizes. Several designs reproduce the structure and native-like properties of the wild-type, while increasing the thermal stability. Other designs, either with similar sizes but different shapes, or with decreased sizes of the packing residues, destabilize the protein. Finally, overpacking the core with the larger side chains causes a loss of native-like structure. These results allow us to further define the roles of tight residue packing and the burial of hydrophobic surface area in the construction of native-like proteins.
在此，我们描述了蛋白质疏水核心的系统性重新设计如何改变其结构和稳定性。我们用改变的堆积模式以及各种不同的侧链形状和大小对四螺旋束蛋白Rop的疏水核心进行了重新包装。几种设计重现了野生型的结构和类似天然的性质，同时提高了热稳定性。其他设计，要么具有相似的大小但不同的形状，要么堆积残基的大小减小，则会使蛋白质不稳定。最后，用较大的侧链过度填充核心会导致类似天然结构的丧失。这些结果使我们能够进一步确定紧密的残基堆积和疏水表面积的埋藏在构建类似天然蛋白质中的作用。
