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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Direct inter-subdomain interactions switch between the closed and open forms of the Hsp70 nucleotide-binding domain in the nucleotide-free state.
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Direct inter-subdomain interactions switch between the closed and open forms of the Hsp70 nucleotide-binding domain in the nucleotide-free state.

机译：直接inter-subdomain交互之间切换Hsp70的封闭和开放的形式nucleotide-free nucleotide-binding域状态。

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摘要

The 70 kDa heat-shock proteins (Hsp70s) are highly conserved chaperones that are involved in several cellular processes, such as protein folding, disaggregation and translocation. In this study, the crystal structures of the human Hsp70 nucleotide-binding domain (NBD) fragment were determined in the nucleotide-free state and in complex with adenosine 5'-(beta,gamma-imido)triphosphate (AMPPNP). The structure of the nucleotide-free NBD fragment is similar to that of the AMPPNP-bound NBD fragment and is designated as the ;closed form'. In the nucleotide-free NBD fragment the closed form is intrinsically supported through interactions between Tyr15, Lys56 and Glu268 which connect subdomains IA, IB and IIB at the centre of the protein. Interaction with the substrate-binding domain (SBD) of Hsp70 or the BAG domain of BAG1 impairs this subdomain connection and triggers the rotation of subdomain IIA around a hydrophobic helix from subdomain IA. The subdomain rotation is limited by Asp199 and Asp206 from subdomain IIA and clearly defines the open form of the NBD. The open form is further stabilized by a new interaction between Gly230 from subdomain IIB and Ser340 from subdomain IIA. The structure of the NBD in the nucleotide-free state is determined by switching of the inter-subdomain interactions.
机译：70 kDa热休克蛋白(Hsp70s)是高度参与几个守恒的陪伴细胞过程,比如蛋白质折叠,解集和易位。人类Hsp70的晶体结构nucleotide-binding域(NBD)片段在nucleotide-free状态和决定复杂与腺苷5 ' -三磷酸(β,gamma-imido) (AMPPNP)。nucleotide-free NBD片段的结构类似于AMPPNP-bound NBD片段并被指定为;闭型”。nucleotide-free NBD片段封闭的形式本质上支持通过交互介于Tyr15 Lys56 Glu268连接子域IA、IB和IIB的中心蛋白质。域(作为)Hsp70或袋BAG1领域削弱这个子域连接和触发器子域名的旋转周围活动花絮从子域名IA疏水螺旋。子域名Asp199和旋转是有限的Asp206子域名花絮和清楚地定义了NBD开放形式。稳定在一个新的Gly230之间的交互从IIB子域和子域Ser340花絮。nucleotide-free NBD的结构是由开关的状态inter-subdomain交互。

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