The Logic of Thermodynamics

Dill, Ken A.; Bromberg, Sarina; Stigter, Dirk

doi:10.4324/9780203809075-7

Cited by 34 publications

(51 citation statements)

References 1 publication

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“…Our discoveries enlarge the scope of the role that soft matter plays in key biological phenomena. Already having detailed the influences of membrane curvature stress in GPCR function ( 25 , 28 ), we now describe an equally powerful biological influence in the form of the bulk solvent ( 85 ). It is important to appreciate the fundamental distinction between these two: the osmotic stress effect must be a result of protein dehydration apart from osmotic dehydration of the lipid bilayer.…”

Section: Discussionmentioning

confidence: 99%

Hydration-mediated G-protein–coupled receptor activation

Fried

Hewage

Eitel

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance Although G-protein–coupled receptors (GPCRs) control vast physiological pathways, their activation remains chemically and physically enigmatic. Our osmotic stress studies of the visual receptor rhodopsin have redefined the standard model of GPCR signaling by revealing the essential role of bulk water. We show results consistent with a large number of water molecules flooding the rhodopsin interior during activation to stabilize the effector binding conformation. These results suggest a model of GPCR activation in which the receptor becomes solvent-swollen upon formation of the active state. We thus demonstrate the mechanism whereby water acts as a powerful allosteric modulator of a pharmacologically important membrane protein family.

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Section: Discussionmentioning

confidence: 99%

Hydration-mediated G-protein–coupled receptor activation

Fried

Hewage

Eitel

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…The unfolding proceeds similar to the well-known coil-globule (CG) transition (SI Fig. 1) (39). Here, the number of transposons at which the CG transition occurs (transition point) depends on the cross-linking energy, with weaker cross-linking leading to unfolding at a lower number of transposons.…”

Section: Resultsmentioning

confidence: 53%

Clustered transposon insertion via formation of chromatin loops

Prizak

Hilbert

2022

Preprint

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Transposons, which are DNA sequences that can move to new positions in the genome, make up a large fraction of eukaryotic genomes and occur in clusters. The insertion of transposons into the genome is hindered by compact folding of chromatin, supposedly preventing aberrant or even pathogenic insertion. Chromatin can, however, be decompacted as a consequence of transposon insertion, leading to increased accessibility and, in consequence, further insertions. While these observations suggest a positive feedback between chromatin unfolding and transposon insertion, how such a feedback might contribute to clustered transposon insertion remains poorly understood. In this study, we analyze polymer models of a self-interacting chromatin domain that unfolds as increasing numbers of transposons are inserted and block the self-interaction. On the one hand, we find that, if additional transposons are inserted adjacently to already inserted transposons, the unfolding of the chromatin domain changes from a sharp globule-coil transition to a more gradual extension of loops from a core that remains folded. On the other hand, we find that adjacent transposon insertion emerges either when transposases are excluded from densely packed chromatin, or when transposon insertion proceeds very quickly in relation to the thermal equilibration of polymer configurations. We thus derive from our model physical conditions for clustered transposon insertion and the resulting spatial compartmentalization of chromatin. An according role was recently suggested for LINE-1 and Alu repeats, which occur in clusters and drive the mesoscopic compartmentalization of the mammalian genome.

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“…46 The low ionic strength of BRB12 is expected to maximize electrostatic interactions between motors and microtubules; for instance, the Debye length in BRB80 is 0.7 nm in BRB80 and 2 nm in BRB12. 47…”

Section: Resultsmentioning

confidence: 99%

The net charge of the K-loop regulates KIF1A superprocessivity by enhancing microtubule affinity in the one-head-bound state

Zaniewski

Hancock

2022

Preprint

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KIF1A is an essential neuronal transport motor protein known for its superprocessive motility. We determined that superprocessivity of KIF1A dimers originates from a unique structural domain, the lysine rich insertion in loop-12 termed the "K-Loop", which enhances electrostatic interactions between the motor and the microtubule. In 80 mM PIPES buffer, replacing the native loop-12 of KIF1A with that of kinesin-1, resulted in a 6-fold decrease in run length, and adding additional positive charge to loop-12 enhanced the run length. Interestingly, swapping the KIF1A loop-12 into kinesin-1 did not enhance its run length, consistent with the two motor families using different mechanochemical tuning to achieve persistent transport. To investigate the mechanism by which the KIF1A K-loop enhances processivity, we used microtubule pelleting and single molecule dwell times assays in ATP and ADP. First, the microtubule affinity was similar in ATP and in ADP, consistent with the motor spending the majority of its cycle in a weakly-bound state. Second, the microtubule affinity and single-molecule dwell time in ADP were ~4-fold lower in the loop-swap mutant. Thus, the positive charge in loop-12 of KIF1A enhances the run length by stabilizing the motor binding in its vulnerable one-head-bound state. Finally, through a series of mutants with varying positive charge in the K-loop, we found that the KIF1A processivity is linearly dependent on the charge of loop-12.

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The Logic of Thermodynamics

Cited by 34 publications

References 1 publication

Hydration-mediated G-protein–coupled receptor activation

Hydration-mediated G-protein–coupled receptor activation

Clustered transposon insertion via formation of chromatin loops

The net charge of the K-loop regulates KIF1A superprocessivity by enhancing microtubule affinity in the one-head-bound state

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