Gautier Candice, Gianni Stefano
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli" and Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, 00185 Rome, Italy.
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli" and Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, 00185 Rome, Italy.
Biochim Biophys Acta Proteins Proteom. 2022 Nov 1;1870(11-12):140852. doi: 10.1016/j.bbapap.2022.140852. Epub 2022 Aug 31.
PDZ domains are highly abundant protein-protein interaction modules in human. One of the most extensively characterized PDZ domain, the third PDZ domain from PSD-95 (PDZ3), contains an α-helical C-terminal extension that has a key role in the function of the domain. Here we compared the folding of PDZ3 with a truncated variant (PDZ3Δα3), lacking the additional helix, by means of the so-called Φ-value analysis, an experimental technique that allows inferring the structure of folding transition states. Experiments reveal subtle but detectable differences in the folding of PDZ3Δα3 versus PDZ3, as probed by structural characterization of the folding transition states. These differences appear more remarkable in the early stages of folding, with a detectable shift of the folding nucleus. The presented results allow demonstrating that the native state exerts a weak bias at the early stages of folding, which appear to be characterized by alternative pathways.
PDZ结构域是人类中高度丰富的蛋白质-蛋白质相互作用模块。研究最广泛的PDZ结构域之一，即PSD-95的第三个PDZ结构域（PDZ3），包含一个α螺旋C端延伸，该延伸在该结构域的功能中起关键作用。在这里，我们通过所谓的Φ值分析（一种允许推断折叠过渡态结构的实验技术），比较了PDZ3与缺乏额外螺旋的截短变体（PDZ3Δα3）的折叠情况。实验揭示了通过折叠过渡态的结构表征探测到的PDZ3Δα3与PDZ3折叠中细微但可检测到的差异。这些差异在折叠早期显得更为显著，折叠核心有可检测到的位移。给出的结果表明，天然态在折叠早期施加了微弱的偏向，这似乎以替代途径为特征。
