PDBsum entry 4nh0

Cell cycle

PDB id: 4nh0

Contents

Protein chains

861 a.a.

Ligands

SO4 ×2

ATP ×4

Metals

_MG ×4

Waters ×8

References listed in PDB file

Key reference

• Title: Substrates control multimerization and activation of the multi-Domain atpase motor of type VII secretion.
• Authors: O.S.Rosenberg, D.Dovala, X.Li, L.Connolly, A.Bendebury, J.Finer-Moore, J.Holton, Y.Cheng, R.M.Stroud, J.S.Cox.
• Ref.: Cell, 2015, 161, 501-512. [DOI no: 10.1016/j.cell.2015.03.040]
• PubMed id: 25865481

Abstract

Mycobacterium tuberculosis and Staphylococcus aureus secrete virulence factors via type VII protein secretion (T7S), a system that intriguingly requires all of its secretion substrates for activity. To gain insights into T7S function, we used structural approaches to guide studies of the putative translocase EccC, a unique enzyme with three ATPase domains, and its secretion substrate EsxB. The crystal structure of EccC revealed that the ATPase domains are joined by linker/pocket interactions that modulate its enzymatic activity. EsxB binds via its signal sequence to an empty pocket on the C-terminal ATPase domain, which is accompanied by an increase in ATPase activity. Surprisingly, substrate binding does not activate EccC allosterically but, rather, by stimulating its multimerization. Thus, the EsxB substrate is also an integral T7S component, illuminating a mechanism that helps to explain interdependence of substrates, and suggests a model in which binding of substrates modulates their coordinate release from the bacterium.