Cortajarena Aitziber L, Kajander Tommi, Pan Weilan, Cocco Melanie J, Regan Lynne
Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208114, New Haven, CT 06520-8114, USA.
Protein Eng Des Sel. 2004 Apr;17(4):399-409. doi: 10.1093/protein/gzh047. Epub 2004 May 27.
Protein design aims to understand the fundamentals of protein structure by creating novel proteins with pre-specified folds. An equally important goal is to understand protein function by creating novel proteins with pre-specified activities. Here we describe the design and characterization of a tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct, short-range protein-peptide interactions and of long-range electrostatic optimization. We demonstrate that the designed protein binds specifically to the desired peptide and discriminates between it and the similar C-terminal peptide of Hsp70.
蛋白质设计旨在通过创建具有预先指定折叠结构的新型蛋白质来理解蛋白质结构的基本原理。一个同样重要的目标是通过创建具有预先指定活性的新型蛋白质来理解蛋白质功能。在此，我们描述了一种四肽重复序列（TPR）蛋白的设计与表征，该蛋白可与真核伴侣蛋白Hsp90的C末端肽结合。该设计强调了直接的短程蛋白质 - 肽相互作用以及长程静电优化的重要性。我们证明，所设计的蛋白质能特异性地结合到所需的肽上，并能区分它与Hsp70的相似C末端肽。
