Dadlez M
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa.
Biochemistry. 1997 Mar 11;36(10):2788-97. doi: 10.1021/bi962407f.
Bovine pancreatic trypsin inhibitor (BPTI) has long served as an important model system for the studies of the protein folding process. Recently a kinetically important folding intermediate has been detected early on the oxidative folding pathway of BPTI [Dadlez, M., & Kim, P. S. (1995) Nat. Struct. Biol. 2, 674-679]. The intermediate, named [14-38], contains a single native disulfide bond between residues 14 and 38, and forms much faster than any other single-disulfide intermediate. A series of 24 mutants of BPTI has been studied here to detect amino acids which contribute to fast formation of [14-38]. Seven nonpolar or aromatic residues, distant from the cysteines by as many as eight residues, are found to accelerate the formation of 14-38 disulfide, without changing the reactivities of the cysteines. The acceleration is observed even in 8 M urea. It is concluded that in the early stages of the folding of BPTI and BPTI-like domains, the residual structure of the denatured state promotes native pairing of cysteines by way of interaction of hydrophobic residues. A similar mechanism may facilitate early steps in the folding of proteins in general.
牛胰蛋白酶抑制剂（BPTI）长期以来一直是研究蛋白质折叠过程的重要模型系统。最近，在BPTI的氧化折叠途径早期检测到了一种动力学上重要的折叠中间体[达德莱兹，M.，& 金，P. S.（1995年）《自然结构生物学》2，674 - 679]。该中间体名为[14 - 38]，在残基14和38之间含有一个单一的天然二硫键，其形成速度比任何其他单二硫键中间体都要快得多。这里研究了一系列24个BPTI突变体，以检测有助于快速形成[14 - 38]的氨基酸。发现有七个非极性或芳香族残基，与半胱氨酸相距多达八个残基，它们能加速14 - 38二硫键的形成，而不改变半胱氨酸的反应活性。即使在8 M尿素中也能观察到这种加速现象。得出的结论是，在BPTI和BPTI样结构域折叠的早期阶段，变性状态的残余结构通过疏水残基的相互作用促进半胱氨酸的天然配对。一般来说，类似的机制可能有助于蛋白质折叠的早期步骤。
