通过独特的蛋白质和蛋白质构象来规范生理和疾病状态。

Specification of Physiologic and Disease States by Distinct Proteins and Protein Conformations.

机构信息

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.

Ann Romney Center for Neurologic Disease, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

出版信息

Cell. 2017 Nov 16;171(5):1001-1014. doi: 10.1016/j.cell.2017.10.047.

DOI:10.1016/j.cell.2017.10.047

PMID:29149602

Abstract

Protein conformational states-from intrinsically disordered ensembles to amyloids that underlie the self-templating, infectious properties of prion-like proteins-have attracted much attention. Here, we highlight the diversity, including differences in biophysical properties, that drive distinct biological functions and pathologies among self-templating proteins. Advances in chemical genomics, gene editing, and model systems now permit deconstruction of the complex interplay between these protein states and the host factors that react to them. These methods reveal that conformational switches modulate normal and abnormal information transfer and that intimate relationships exist between the intrinsic function of proteins and the deleterious consequences of their misfolding.

摘要

蛋白质构象状态——从固有无序的集合到淀粉样纤维，这些都是朊病毒样蛋白自我模板化、传染性的基础——引起了广泛关注。在这里，我们强调了多样性，包括在生物物理特性方面的差异，这些差异驱动了自我模板化蛋白的不同生物学功能和病理学。化学基因组学、基因编辑和模型系统的进展现在允许对这些蛋白质状态与宿主因子之间的复杂相互作用进行解构。这些方法表明构象转换调节正常和异常信息传递，并且蛋白质的固有功能与其错误折叠的有害后果之间存在密切关系。