Perham Michael, Chen Mingzhi, Ma Jianpeng, Wittung-Stafshede Pernilla
Department of Chemistry, Rice University, Houston, Texas 77030, USA.
J Am Chem Soc. 2005 Nov 30;127(47):16402-3. doi: 10.1021/ja055574o.
Protein recognition and binding play a fundamental role in living systems but sometimes also result in pathological aggregates. To probe the coupling between folding and binding in a homoheptameric system, we have characterized the time-resolved unfolding/disassembly mechanism of human co-chaperonin protein 10 (cpn10) by a combination of experimental and computational methods. The results from both approaches are in excellent agreement and make obvious that the kinetic process is three-state: an initial polypeptide-unfolding step, resulting in a non-native heptamer, is followed by a slower heptamer-dissociation step. This demonstrates that the barriers on the kinetic free-energy landscape are defined by thermodynamic stability. cpn10 is one of few, and the only heptameric, experimentally characterized system that follows the "fly casting scenario" of molecular recognition.
蛋白质识别与结合在生命系统中发挥着基础性作用，但有时也会导致病理性聚集体的形成。为了探究同七聚体系统中折叠与结合之间的耦合关系，我们通过实验和计算方法相结合的方式，对人共伴侣蛋白10（cpn10）的时间分辨解折叠/解离机制进行了表征。两种方法得到的结果高度一致，且明确显示动力学过程为三态：首先是多肽解折叠步骤，形成非天然七聚体，随后是较慢的七聚体解离步骤。这表明动力学自由能景观上的障碍是由热力学稳定性决定的。cpn10是少数几个且是唯一经过实验表征的遵循分子识别“抛锚式模式”的七聚体系统之一。
