4NH0

Cytoplasmic domain of the Thermomonospora curvata Type VII Secretion ATPase EccC

Summary for 4NH0

• Entry DOI: 10.2210/pdb4nh0/pdb
• Descriptor: Cell divisionFtsK/SpoIIIE, SULFATE ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: atpase, secretion, esxb, cell cycle
• Biological source: Thermomonospora curvata
• Total number of polymer chains: 2
• Total formula weight: 255266.82

Authors

Rosenberg, O.S.,Cox, J.S.,Stroud, R.M.,Strauli, N.,Dovala, D. (deposition date: 2013-11-03, release date: 2015-02-11, Last modification date: 2024-02-28)

Primary citation

Rosenberg, O.S.,Dovala, D.,Li, X.,Connolly, L.,Bendebury, A.,Finer-Moore, J.,Holton, J.,Cheng, Y.,Stroud, R.M.,Cox, J.S.
Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion.
Cell(Cambridge,Mass.), 161:501-512, 2015

PubMed 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.

PubMed: 25865481
DOI: 10.1016/j.cell.2015.03.040

Experimental method

X-RAY DIFFRACTION (2.9 Å)