ATP hydrolysis-coupled peptide translocation mechanism of Mycobacterium tuberculosis ClpB

• DOI: 10.1073/pnas.1810648115
• Publication Date: 2018-09-26T20:06:03Z
• Authors: Hongjun Yu; Tania J. Lupoli; Amanda Kovach; Xing Meng; Gongpu Zhao; Carl F. Nathan; Huilin Li
• Keywords: 0301 basic medicine; Protein Transport; 03 medical and health sciences; Adenosine Triphosphate; PNAS Plus; Bacterial Proteins; Protein Domains; Hydrolysis; Endopeptidase Clp; Mycobacterium tuberculosis; 3. Good health

Significance

The Mycobacterium tuberculosis ( Mtb ) ClpB is a ring-shaped, ATP-driven disaggregase. The ability to rescue aggregated proteins is crucial for Mtb to grow and persist in the host. Despite extensive studies in the past two decades, it is still not well understood how a bacterial disaggregase couples ATP binding and hydrolysis to peptide translocation. Our cryo-EM study of the Mtb ClpB in the presence of a peptide substrate and the slowly hydrolysable adenosine 5′-[γ-thio]triphosphate revealed two active conformations in the midst of the substrate-threading process. This, together with the resolved nucleotide state in each of the 12 nucleotide-binding domains of the ClpB hexamer, helps define a detailed atomic trajectory that couples ATP binding and hydrolysis to mechanical protein translocation.