Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion
Abstract
We report that 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.
- Authors:
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1392135
- Alternate Identifier(s):
- OSTI ID: 1178832
- Grant/Contract Number:
- AC02-06CH11357; AC02-05CH11231; P41GM103393
- Resource Type:
- Journal Article: Published Article
- Journal Name:
- Cell
- Additional Journal Information:
- Journal Name: Cell Journal Volume: 161 Journal Issue: 3; Journal ID: ISSN 0092-8674
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Rosenberg, Oren S., Dovala, Dustin, Li, Xueming, Connolly, Lynn, Bendebury, Anastasia, Finer-Moore, Janet, Holton, James, Cheng, Yifan, Stroud, Robert M., and Cox, Jeffery S. Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion. United States: N. p., 2015.
Web. doi:10.1016/j.cell.2015.03.040.
Rosenberg, Oren S., Dovala, Dustin, Li, Xueming, Connolly, Lynn, Bendebury, Anastasia, Finer-Moore, Janet, Holton, James, Cheng, Yifan, Stroud, Robert M., & Cox, Jeffery S. Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion. United States. https://doi.org/10.1016/j.cell.2015.03.040
Rosenberg, Oren S., Dovala, Dustin, Li, Xueming, Connolly, Lynn, Bendebury, Anastasia, Finer-Moore, Janet, Holton, James, Cheng, Yifan, Stroud, Robert M., and Cox, Jeffery S. 2015.
"Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion". United States. https://doi.org/10.1016/j.cell.2015.03.040.
@article{osti_1392135,
title = {Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion},
author = {Rosenberg, Oren S. and Dovala, Dustin and Li, Xueming and Connolly, Lynn and Bendebury, Anastasia and Finer-Moore, Janet and Holton, James and Cheng, Yifan and Stroud, Robert M. and Cox, Jeffery S.},
abstractNote = {We report that 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.},
doi = {10.1016/j.cell.2015.03.040},
url = {https://www.osti.gov/biblio/1392135},
journal = {Cell},
issn = {0092-8674},
number = 3,
volume = 161,
place = {United States},
year = {Wed Apr 01 00:00:00 EDT 2015},
month = {Wed Apr 01 00:00:00 EDT 2015}
}
Web of Science
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