Novel polychromogenic fluorine-substituted spiropyrans demonstrating either uni- or bidirectional photochromism as multipurpose molecular switches

AbstractMycobacterium tuberculosis secretes the tuberculosis necrotizing toxin (TNT) to kill host cells. Here, we show that the WXG100 proteins EsxE and EsxF are essential for TNT secretion. EsxE and EsxF form a water-soluble heterodimer (EsxEF) that assembles into oligomers and long filaments, binds to membranes, and forms stable membrane-spanning channels. Electron microscopy of EsxEF reveals mainly pentameric structures with a central pore. Mutations of both WXG motifs and of a GXW motif do not affect dimerization, but abolish pore formation, membrane deformation and TNT secretion. The WXG/GXW mutants are locked in conformations with altered thermostability and solvent exposure, indicating that the WXG/GXW motifs are molecular switches controlling membrane interaction and pore formation. EsxF is accessible on the bacterial cell surface, suggesting that EsxEF form an outer membrane channel for toxin export. Thus, our study reveals a protein secretion mechanism in bacteria that relies on pore formation by small WXG proteins.

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PAK and other Rho-associated kinases – effectors with surprisingly diverse mechanisms of regulation

Biochemical Journal ◽

10.1042/bj20041638 ◽

2005 ◽

Vol 386 (2) ◽

pp. 201-214 ◽

Cited By ~ 190

Author(s):

Zhou-shen ZHAO ◽

Ed MANSER

Keyword(s):

Rho Gtpases ◽

Cell Biology ◽

Rho Gtpase ◽

Rho Kinase ◽

Molecular Switches ◽

Eukaryotic Cell ◽

Effector Proteins ◽

Downstream Effector ◽

P21 Activated Kinase ◽

Do So

The Rho GTPases are a family of molecular switches that are critical regulators of signal transduction pathways in eukaryotic cells. They are known principally for their role in regulating the cytoskeleton, and do so by recruiting a variety of downstream effector proteins. Kinases form an important class of Rho effector, and part of the biological complexity brought about by switching on a single GTPase results from downstream phosphorylation cascades. Here we focus on our current understanding of the way in which different Rho-associated serine/threonine kinases, denoted PAK (p21-activated kinase), MLK (mixed-lineage kinase), ROK (Rho-kinase), MRCK (myotonin-related Cdc42-binding kinase), CRIK (citron kinase) and PKN (protein kinase novel), interact with and are regulated by their partner GTPases. All of these kinases have in common an ability to dimerize, and in most cases interact with a variety of other proteins that are important for their function. A diversity of known structures underpin the Rho GTPase–kinase interaction, but only in the case of PAK do we have a good molecular understanding of kinase regulation. The ability of Rho GTPases to co-ordinate spatial and temporal phosphorylation events explains in part their prominent role in eukaryotic cell biology.

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Synthesis of fluorescent molecular switches based on porphyrinoids covalently linked with redox active ligands

Journal of Molecular Structure ◽

10.1016/j.molstruc.2021.131407 ◽

2022 ◽

Vol 1247 ◽

pp. 131407

Author(s):

Kharu Nisa ◽

Gaurav Kumar Mishra ◽

M. Thirumal ◽

Shive M.S. Chauhan

Keyword(s):

Molecular Switches ◽

Redox Active Ligands ◽

Redox Active ◽

Covalently Linked

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Phosphorylation: The Molecular Switch of Double-Strand Break Repair

International Journal of Proteomics ◽

10.1155/2011/373816 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 24

Author(s):

K. C. Summers ◽

F. Shen ◽

E. A. Sierra Potchanant ◽

E. A. Phipps ◽

R. J. Hickey ◽

...

Keyword(s):

Mammalian Cells ◽

Genomic Stability ◽

Molecular Switches ◽

Strand Break ◽

Nonhomologous End Joining ◽

End Joining ◽

Brca1 And Brca2 ◽

Damage Response ◽

Repair Mechanisms ◽

Repair Pathways

Repair of double-stranded breaks (DSBs) is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ), homologous recombination (HR), or the inclusive DNA damage response (DDR). These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms.

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ChemInform Abstract: Visible-Light-Activated Molecular Switches

ChemInform ◽

10.1002/chin.201546247 ◽

2015 ◽

Vol 46 (46) ◽

pp. no-no

Author(s):

David Bleger ◽

Stefan Hecht

Keyword(s):

Visible Light ◽

Molecular Switches

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