热休克蛋白 70 在核糖体上的相互作用途径。
Pathway of Hsp70 interactions at the ribosome.
机构信息
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
Department of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, 94158, USA.
出版信息
Nat Commun. 2021 Sep 27;12(1):5666. doi: 10.1038/s41467-021-25930-8.
In eukaryotes, an Hsp70 molecular chaperone triad assists folding of nascent chains emerging from the ribosome tunnel. In fungi, the triad consists of canonical Hsp70 Ssb, atypical Hsp70 Ssz1 and J-domain protein cochaperone Zuo1. Zuo1 binds the ribosome at the tunnel exit. Zuo1 also binds Ssz1, tethering it to the ribosome, while its J-domain stimulates Ssb's ATPase activity to drive efficient nascent chain interaction. But the function of Ssz1 and how Ssb engages at the ribosome are not well understood. Employing in vivo site-specific crosslinking, we found that Ssb(ATP) heterodimerizes with Ssz1. Ssb, in a manner consistent with the ADP conformation, also crosslinks to ribosomal proteins across the tunnel exit from Zuo1. These two modes of Hsp70 Ssb interaction at the ribosome suggest a functionally efficient interaction pathway: first, Ssb(ATP) with Ssz1, allowing optimal J-domain and nascent chain engagement; then, after ATP hydrolysis, Ssb(ADP) directly with the ribosome.
在真核生物中，一个 Hsp70 分子伴侣三聚体协助从核糖体隧道中延伸的新生链折叠。在真菌中，三聚体由典型的 Hsp70 Ssb、非典型的 Hsp70 Ssz1 和 J 结构域蛋白共伴侣 Zuo1 组成。Zuo1 结合在核糖体隧道出口处的核糖体上。Zuo1 还结合 Ssz1，将其连接到核糖体上，而其 J 结构域刺激 Ssb 的 ATP 酶活性以驱动有效的新生链相互作用。但 Ssz1 的功能以及 Ssb 与核糖体结合的方式尚未得到很好的理解。通过体内定点交联实验，我们发现 Ssb(ATP)与 Ssz1 异源二聚化。Ssb 以与 ADP 构象一致的方式，也与 Zuo1 核糖体隧道出口处的核糖体蛋白交联。这种 Hsp70 Ssb 在核糖体上的两种相互作用方式表明了一种功能高效的相互作用途径：首先，Ssb(ATP)与 Ssz1 结合，允许最佳的 J 结构域和新生链结合；然后，在 ATP 水解后，Ssb(ADP)直接与核糖体结合。
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