4LWS

EsxA : EsxB (SeMet) hetero-dimer from Thermomonospora curvata

Summary for 4LWS

• Entry DOI: 10.2210/pdb4lws/pdb
• Descriptor: Uncharacterized protein, ACETATE ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: esx secretion, signal sequence, type vii secretion, unknown function
• Biological source: Thermomonospora curvata; More
• Total number of polymer chains: 2
• Total formula weight: 27597.78

Authors

Dovala, D.L.,Cox, J.S.,Stroud, R.M.,Rosenberg, O.S. (deposition date: 2013-07-28, release date: 2015-02-04, Last modification date: 2024-11-27)

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 Å)