Singh Ajit Kumar, Saharan Ketul, Baral Somanath, Vasudevan Dileep
Institute of Life Sciences, Bhubaneswar 751023, India.
Institute of Life Sciences, Bhubaneswar 751023, India; Regional Centre for Biotechnology, Faridabad 121001, India.
Biochim Biophys Acta Gene Regul Mech. 2022 Oct;1865(7):194872. doi: 10.1016/j.bbagrm.2022.194872. Epub 2022 Sep 2.
The nucleoplasmin family of histone chaperones is a key player in governing the dynamic architecture of chromatin, thereby regulating various DNA-templated processes. The crystal structure of the N-terminal domain of Arabidopsis thaliana FKBP43 (AtFKBP43), an FK506-binding immunophilin protein, revealed a characteristic nucleoplasmin fold, thus confirming it to be a member of the FKBP nucleoplasmin class. Small-Angle X-ray Scattering (SAXS) analyses confirmed its pentameric nature in solution, and additional studies confirmed the nucleoplasmin fold to be highly stable. Unlike its homolog AtFKBP53, the AtFKBP43 nucleoplasmin core domain could not interact with histones and required the acidic arms, C-terminal to the core, for histone association. However, SAXS generated low-resolution envelope structure, ITC, and AUC results revealed that an AtFKBP43 pentamer with C-terminal extensions interacts with H2A/H2B dimer and H3/H4 tetramer in an equimolar ratio, like AtFKBP53. Put together, AtFKBP43 belongs to a hitherto unreported subclass of FKBP nucleoplasmins that requires the C-terminal acidic stretches emanating from the core domain for histone interaction.
组蛋白伴侣核质蛋白家族在调控染色质的动态结构中起着关键作用，从而调节各种DNA模板化过程。拟南芥FKBP43（AtFKBP43）的N端结构域的晶体结构，AtFKBP43是一种结合FK506的亲免素蛋白，揭示了一种特征性的核质蛋白折叠，从而证实它是FKBP核质蛋白家族的一员。小角X射线散射（SAXS）分析证实了其在溶液中的五聚体性质，进一步的研究证实核质蛋白折叠高度稳定。与其同源物AtFKBP53不同，AtFKBP43核质蛋白核心结构域不能与组蛋白相互作用，需要核心结构域C端的酸性臂来与组蛋白结合。然而，SAXS产生的低分辨率包膜结构、等温滴定量热法（ITC）和分析型超速离心（AUC）结果表明，具有C端延伸的AtFKBP43五聚体与H2A/H2B二聚体和H3/H4四聚体以等摩尔比相互作用，与AtFKBP53类似。综上所述，AtFKBP43属于FKBP核质蛋白中一个迄今未报道的亚类，该亚类需要核心结构域发出的C端酸性延伸来与组蛋白相互作用。
