The crystal structure of the Mycobacterium tuberculosis Rv3019c-Rv3020c ESX complex reveals a domain-swapped heterotetramer.

Protein Science : a Publication of the Protein Society
Mark A ArbingDavid Eisenberg

Abstract

Mycobacterium tuberculosis encodes five gene clusters (ESX-1 to ESX-5) for Type VII protein secretion systems that are implicated in mycobacterial pathogenicity. Substrates for the secretion apparatus are encoded within the gene clusters and in additional loci that lack the components of the secretion apparatus. The best characterized substrates are the ESX complexes, 1:1 heterodimers of ESAT-6 and CFP-10, the prototypical member that has been shown to be essential for Mycobacterium tuberculosis pathogenesis. We have determined the structure of EsxRS, a homolog of EsxGH of the ESX-3 gene cluster, at 1.91 Å resolution. The EsxRS structure is composed of two four-helix bundles resulting from the 3D domain swapping of the C-terminal domain of EsxS, the CFP-10 homolog. The four-helix bundles at the extremities of the complex have a similar architecture to the structure of ESAT-6·CFP-10 (EsxAB) of ESX-1, but in EsxRS a hinge loop linking the α-helical domains of EsxS undergoes a loop-to-helix transition that creates the domain swapped EsxRS tetramer. Based on the atomic structure of EsxRS and existing biochemical data on ESX complexes, we propose that higher order ESX oligomers may increase avidity of ESX binding to host receptor mo...Continue Reading

References

Feb 14, 1971·Journal of Molecular Biology·B Lee, F M Richards
Dec 20, 1993·Journal of Molecular Biology·M C Lawrence, P M Colman
Sep 1, 1993·Protein Science : a Publication of the Protein Society·C Colovos, T O Yeates
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·T C Terwilliger, J Berendzen
May 20, 1999·Nature Structural Biology·A PerrakisV S Lamzin
Mar 1, 2000·Tubercle and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·F TekaiaS T Cole
Sep 12, 2000·Bioinformatics·L Holm, J Park
Nov 22, 2001·Acta Crystallographica. Section D, Biological Crystallography·T C Terwilliger
Apr 26, 2002·Trends in Microbiology·Mark J Pallen
May 22, 2002·Protein Science : a Publication of the Protein Society·Yanshun Liu, David Eisenberg
Jan 1, 2003·The Journal of Infectious Diseases·Kaeryn N LewisDavid R Sherman
Apr 15, 2003·Nature Medicine·Alexander S PymStewart T Cole
Oct 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sarah A StanleyJeffery S Cox
Oct 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Tsungda HsuWilliam R Jacobs
Jun 25, 2004·Nucleic Acids Research·Burkhard RostJinfeng Liu
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Mar 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laleh MajlessiClaude Leclerc
Jul 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·S M FortuneE J Rubin
Sep 2, 2005·Molecular Microbiology·Jason A MacGurnJeffery S Cox
Mar 23, 2006·Acta Crystallographica. Section D, Biological Crystallography·Jay Painter, Ethan A Merritt
May 16, 2006·Structure·Melanie J BennettDavid Eisenberg
May 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Zhefeng Guo, David Eisenberg
Sep 16, 2006·Science·Patricia A Digiuseppe ChampionJeffery S Cox
Nov 14, 2006·Journal of Bacteriology·Anna MaciagRiccardo Manganelli
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Oct 9, 2007·Nature Reviews. Microbiology·Abdallah M AbdallahWilbert Bitter
Jun 17, 2008·Molecular Microbiology·Abbie CorosKeith M Derbyshire
Mar 14, 2009·Annual Review of Pharmacology and Toxicology·Liem Nguyen, Jean Pieters

❮ Previous
Next ❯

Citations

Apr 24, 2013·Applied Biochemistry and Biotechnology·Ai-hua ZhangXi-jun Wang
Nov 4, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Anshuman ShuklaScott A White
May 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Tatyana A SysoevaBriana M Burton
Nov 6, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Thomas A BobikMadeline E Rasche
Aug 14, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Satoshi NagaoShun Hirota
Sep 17, 2013·Molecular Microbiology·Mark AndersonDominique Missiakas
Nov 25, 2016·Protein Science : a Publication of the Protein Society·Masaru YamanakaShun Hirota
Sep 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Do-Hee KimBong-Jin Lee
Aug 8, 2018·FEMS Microbiology Letters·Trang H Phan, Edith N G Houben
Sep 7, 2017·Journal of Bacteriology·Khaled A AlyDominique Missiakas
Jul 15, 2020·Annual Review of Microbiology·Catalin M BunducE N G Houben
Aug 11, 2019·Microbiology Spectrum·Vincent J C van WindenMiriam Braunstein
Mar 22, 2016·Microbiology Spectrum·Louis S AtesWilbert Bitter

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.