Abstract:
:The regulation of protein function through ligand-induced conformational changes is crucial for many signal transduction processes. The binding of a ligand alters the delicate energy balance within the protein structure, eventually leading to such conformational changes. In this study, we elucidate the energetic and mechanical changes within the subdomains of the nucleotide binding domain (NBD) of the heat shock protein of 70 kDa (Hsp70) chaperone DnaK upon nucleotide binding. In an integrated approach using single molecule optical tweezer experiments, loop insertions, and steered coarse-grained molecular simulations, we find that the C-terminal helix of the NBD is the major determinant of mechanical stability, acting as a glue between the two lobes. After helix unraveling, the relative stability of the two separated lobes is regulated by ATP/ADP binding. We find that the nucleotide stays strongly bound to lobe II, thus reversing the mechanical hierarchy between the two lobes. Our results offer general insights into the nucleotide-induced signal transduction within members of the actin/sugar kinase superfamily.
journal_name
Proc Natl Acad Sci U S Aauthors
Bauer D,Merz DR,Pelz B,Theisen KE,Yacyshyn G,Mokranjac D,Dima RI,Rief M,Žoldák Gdoi
10.1073/pnas.1504625112subject
Has Abstractpub_date
2015-08-18 00:00:00pages
10389-94issue
33eissn
0027-8424issn
1091-6490pii
1504625112journal_volume
112pub_type
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