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      Interdomain communication suppressing high intrinsic ATPase activity of Sse1 is essential for its co-disaggregase activity with Ssa1.

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          Abstract

          In eukaryotes, Hsp110s are unambiguous cognates of the Hsp70 chaperones, in primary sequence, domain organization, and structure. Hsp110s function as nucleotide exchange factors (NEFs) for the Hsp70s although their apparent loss of Hsp70-like chaperone activity, nature of interdomain communication, and breadth of domain functions are still puzzling. Here, by combining single-molecule FRET, small angle X-ray scattering measurements (SAXS), and MD simulation, we show that yeast Hsp110, Sse1 lacks canonical Hsp70-like interdomain allostery. However, the protein exhibits unique noncanonical conformational changes within its domains. Sse1 maintains an open-lid substrate-binding domain (SBD) in close contact with its nucleotide-binding domain (NBD), irrespective of its ATP hydrolysis status. To further appreciate such ATP-hydrolysis-independent exhaustive interaction between two domains of Hsp110s, NBD-SBD chimera was constructed between Hsp110 (Sse1) and Hsp70 (Ssa1). In Sse1/Ssa1 chimera, we observed undocking of two domains leading to complete loss of NEF activity of Sse1. Interestingly, chimeric proteins exhibited significantly enhanced ATPase rate of Sse1-NBD compared to wild-type protein, implying that intrinsic ATPase activity of the protein remains mostly repressed. Apart from repressing the high ATPase activity of its NBD, interactions between two domains confer thermal stability to Sse1 and play critical role in the (co)chaperoning function of Sse1 in Ssa1-mediated disaggregation activity. Altogether, Sse1 exhibits a unique interdomain interaction, which is essential for its NEF activity, suppression of high intrinsic ATPase activity, co-chaperoning activity in disaggregase machinery, and stability of the protein.

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          Author and article information

          Journal
          FEBS J
          The FEBS journal
          Wiley
          1742-4658
          1742-464X
          February 2020
          : 287
          : 4
          Affiliations
          [1 ] Proteomics and Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
          [2 ] Academy of Scientific and Innovative Research (AcSir), CSIR-HRDC, Ghaziabad, India.
          [3 ] CSIR-Institute of Microbial Technology, Chandigarh, Uttar Pradesh, India.
          [4 ] Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, India.
          [5 ] Department of Plant Molecular Biology, University of Lausanne, Switzerland.
          Article
          10.1111/febs.15045
          31423733
          699da961-788e-4c2a-bbfb-5629051b12b9
          © 2019 Federation of European Biochemical Societies.
          History

          Hsp110,Hsp70,molecular chaperones,single-molecule FRET,small angle X-ray scattering

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