4LJ6

ClpB NBD2 from T. thermophilus in complex with AMPPCP

Summary for 4LJ6

• Entry DOI: 10.2210/pdb4lj6/pdb
• Related: 4LJ4 4LJ5 4LJ7 4LJ8 4LJ9 4LJA
• Descriptor: Chaperone protein ClpB, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: aaa+ protein, nucleotide binding domain, molecular chaperone, disaggregase, chaperone
• Biological source: Thermus thermophilus
• Cellular location: Cytoplasm : Q9RA63
• Total number of polymer chains: 1
• Total formula weight: 38958.18

Authors

Zeymer, C.,Barends, T.R.M.,Werbeck, N.D.,Schlichting, I.,Reinstein, J. (deposition date: 2013-07-04, release date: 2014-02-12, Last modification date: 2023-11-08)

Primary citation

Zeymer, C.,Barends, T.R.M.,Werbeck, N.D.,Schlichting, I.,Reinstein, J.
Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor
Acta Crystallogr.,Sect.D, 70:582-595, 2014

PubMed Abstract: ATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg2+ ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis.

PubMed: 24531492
DOI: 10.1107/S1399004713030629

Experimental method

X-RAY DIFFRACTION (1.9 Å)