Rajasekaran Nandakumar, Kaiser Christian M
CMDB Graduate Program, Johns Hopkins University, Baltimore, MD, United States.
Department of Biology, Johns Hopkins University, Baltimore, MD, United States.
Front Mol Biosci. 2022 Apr 20;9:869027. doi: 10.3389/fmolb.2022.869027. eCollection 2022.
The majority of proteins in nature are composed of multiple domains connected in a single polypeptide. How these long sequences fold into functional structures without forming toxic misfolds or aggregates is poorly understood. Their folding is inextricably linked to protein synthesis and interactions with cellular machinery, making mechanistic studies challenging. Recent progress has revealed critical features of multi-domain protein folding in isolation and in the context of translation by the ribosome. In this review, we discuss challenges and progress in understanding multi-domain protein folding, and highlight how molecular interactions shape folding and misfolding pathways. With the development of new approaches and model systems, the stage is now set for mechanistically exploring the folding of large multi-domain proteins.
自然界中的大多数蛋白质由连接在一条多肽链中的多个结构域组成。这些长序列如何折叠成功能结构而不形成有毒的错误折叠或聚集体，目前还知之甚少。它们的折叠与蛋白质合成以及与细胞机制的相互作用紧密相连，这使得机理研究颇具挑战性。最近的进展揭示了多结构域蛋白质在孤立状态下以及在核糖体翻译过程中的关键折叠特征。在这篇综述中，我们讨论了在理解多结构域蛋白质折叠方面的挑战和进展，并强调了分子相互作用如何塑造折叠和错误折叠途径。随着新方法和模型系统的发展，现在已为从机理上探索大型多结构域蛋白质的折叠奠定了基础。
