PERSPECTIVE: EMBEDDED MOLECULAR SWITCHES, ANTICANCER SELECTION, AND EFFECTS ON ONTOGENETIC RATES: A HYPOTHESIS OF DEVELOPMENTAL CONSTRAINT ON MORPHOGENESIS AND EVOLUTION

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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Cost of autotomy drives ontogenetic switching of anti-predator mechanisms under developmental constraints in a land snail

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2012.1943 ◽

2012 ◽

Vol 279 (1748) ◽

pp. 4811-4816 ◽

Cited By ~ 11

Author(s):

Masaki Hoso

Keyword(s):

High Efficiency ◽

Shell Growth ◽

Land Snail ◽

Life History Strategies ◽

Body Parts ◽

Developmental Constraint ◽

Developmental Constraints ◽

Evolution Of Life ◽

Snake Range ◽

In The Wild

Autotomy of body parts offers various prey animals immediate benefits of survival in compensation for considerable costs. I found that a land snail Satsuma caliginosa of populations coexisting with a snail-eating snake Pareas iwasakii survived the snake predation by autotomizing its foot, whereas those out of the snake range rarely survived. Regeneration of a lost foot completed in a few weeks but imposed a delay of shell growth. Imprints of autotomy were found in greater than 10 per cent of S. caliginosa in the snake range but in only less than 1 per cent out of it, simultaneously demonstrating intense predation by the snakes and high efficiency of autotomy for surviving snake predation in the wild. However, in experiments, mature S. caliginosa performed autotomy less frequently. Instead of the costly autotomy, they can use defensive denticles on the inside of their shell apertures. Owing to the constraints from the additive growth of shells, most pulmonate snails can produce these denticles only when they have fully grown up. Thus, this developmental constraint limits the availability of the modified aperture, resulting in ontogenetic switching of the alternative defences. This study illustrates how costs of adaptation operate in the evolution of life-history strategies under developmental constraints

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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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