烟曲霉亲环蛋白的晶体结构揭示了一个中心元件的三维结构域交换。

The crystal structure of Aspergillus fumigatus cyclophilin reveals 3D domain swapping of a central element.

作者信息

Limacher Andreas, Kloer Daniel P, Flückiger Sabine, Folkers Gerd, Crameri Reto, Scapozza Leonardo

机构信息

Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.

出版信息

Structure. 2006 Feb;14(2):185-95. doi: 10.1016/j.str.2005.10.015.

DOI:10.1016/j.str.2005.10.015

PMID:16472738

Abstract

The crystal structure of Aspergillus fumigatus cyclophilin (Asp f 11) was solved by the multiwavelength anomalous dispersion method and was refined to a resolution of 1.85 A with R and R(free) values of 18.9% and 21.4%, respectively. Many cyclophilin structures have been solved to date, all showing the same monomeric conformation. In contrast, the structure of A. fumigatus cyclophilin reveals dimerization by 3D domain swapping and represents one of the first proteins with a swapped central domain. The domain-swapped element consists of two beta strands and a subsequent loop carrying a conserved tryptophan. The tryptophan binds into the active site, inactivating cis-trans isomerization. This might be a means of biological regulation. The two hinge loops leave the protein prone to misfolding. In this context, alternative forms of 3D domain swapping that can lead to N- or C-terminally swapped dimers, oligomers, and aggregates are discussed.

摘要

烟曲霉亲环蛋白（Asp f 11）的晶体结构通过多波长反常色散法解析，并精修至1.85埃的分辨率，R值和R（自由）值分别为18.9%和21.4%。迄今为止，许多亲环蛋白的结构已被解析，均呈现相同的单体构象。相比之下，烟曲霉亲环蛋白的结构通过三维结构域交换形成二聚体，是首批具有结构域交换中心结构域的蛋白质之一。结构域交换元件由两条β链和一个带有保守色氨酸的后续环组成。色氨酸结合到活性位点，使顺反异构化失活。这可能是一种生物调节方式。两个铰链环使该蛋白质易于错误折叠。在此背景下，还讨论了可导致N端或C端结构域交换二聚体、寡聚体和聚集体的三维结构域交换的其他形式。