Association and dissociation kinetics of colicin E3 and immunity protein 3: Convergence of theory and experiment

Zhou, Huan‐Xiang

doi:10.1110/ps.03216203

Cited by 27 publications

(28 citation statements)

References 23 publications

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“…These decreases in k a are comparable with those presented above for the binding constant K a . The similar effects of ionic strength on k a and K a have been observed on many protein-protein complexes (8,18,19) and also on protein-RNA complexes (20,21). This widely observed phenomenon has been explained within the transient-complex theory, in that the transient complex is structurally close to the native complex and therefore experiences salt screening to nearly the same extent (18,19).…”

Section: Resultssupporting

confidence: 65%

Dissection of the high rate constant for the binding of a ribotoxin to the ribosome

Qin

Zhou

2009

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

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Restrictocin belongs to a family of site-specific ribonucleases that kill cells by inactivating the ribosome. The restrictocin–ribosome binding rate constant was observed to exceed 1010 M−1 s−1. We have developed a transient-complex theory to model the binding rates of protein–protein and protein–RNA complexes. The theory predicts the rate constant as ka = ka0 exp(−ΔGel*/kBT), where ka0 is the basal rate constant for reaching the transient complex, located at the outer boundary of the bound state, by random diffusion, and ΔGel* is the average electrostatic interaction free energy of the transient complex. Here, we applied the transient-complex theory to dissect the high restrictocin–ribosome binding rate constant. We found that the binding rate of restrictocin to the isolated sarcin/ricin loop is electrostatically enhanced by ≈300-fold, similar to results found in other protein–protein and protein–RNA complexes. The ribosome provides an additional 10,000-fold rate enhancement because of two synergistic mechanisms afforded by the distal regions of the ribosome. First, they provide additional electrostatic attraction with restrictocin. Second, they reposition the transient complex into a region where local electrostatic interactions of restrictocin with the sarcin/ricin loop are particularly favorable. Our calculations rationalize a host of experimental observations and identify a strategy for designing proteins that bind their targets with high speed.

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Section: Resultssupporting

confidence: 65%

Dissection of the high rate constant for the binding of a ribotoxin to the ribosome

Qin

Zhou

2009

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

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“…While this result demonstrates that electrostatic interactions are also important for maintaining the Spy-Im7 A3W complex, they appear to play a more critical role in complex formation. Such differences in the ionic strength dependence of binding and release rate constants have been reported for a number of other protein-protein interactions (Darling et al, 2002; Hemsath et al, 2005; Joachimiak et al, 2014; Kirchhoff et al, 1997; Schreiber and Fersht, 1993; Wallis et al, 1995; Zhou, 2001, 2003). Our results suggest that the forces governing unfolded Im7 binding and release are at least partially different.…”

Section: Resultssupporting

confidence: 56%

Forces Driving Chaperone Action

Koldewey

Stull

Horowitz

et al. 2016

Cell

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SUMMARY It is still unclear what molecular forces drive chaperone-mediated protein folding. Here, we obtain a detailed mechanistic understanding of the forces that dictate the four key steps of chaperone-client interaction: initial binding, complex stabilization, folding, and release. Contrary to the common belief that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7. Short-range hydrophobic interactions follow, which serve to stabilize the complex. Hydrophobic collapse of the client protein then drives its folding. By burying hydrophobic residues in its core, the client’s affinity to Spy decreases, which causes client release. By allowing the client to fold itself, Spy circumvents the need for client-specific folding instructions. This mechanism might help explain how chaperones can facilitate the folding of various unrelated proteins.

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“…This indicates a fast exchange dynamics between monomers and heterodimers. Fast association/dissociation events have been found for several binding interfaces that are largely electrostatic by nature (Gabdoulline and Wade, 2001; Schreiber and Fersht, 1996; Zhou, 2003). Slower processes are associated with the release or solvation of hydrophobic side chains and these appear to be minimized in the structure of this complex.…”

Section: Discussionmentioning

confidence: 99%

NMR Structure of a Heterodimeric SAM:SAM Complex: Characterization and Manipulation of EphA2 Binding Reveal New Cellular Functions of SHIP2

et al. 2012

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The sterile alpha motif (SAM) for protein-protein interactions is encountered in over 200 proteins, but the structural bases for its interactions is just becoming clear. Here we solved the structure of the EphA2-SHIP2 SAM:SAM heterodimeric complex by use of NMR restraints from chemical shift perturbations, NOE and RDC experiments. Specific contacts between the protein surfaces differ significantly from a previous model and from other SAM:SAM complexes. Molecular dynamics and docking simulations indicate fluctuations in the complex towards alternate, higher energy conformations. The interface suggests that EphA family members bind to SHIP2 SAM whereas EphB members may not; correspondingly we demonstrate binding of EphA1 but not of EphB2 to SHIP2 SAM. A variant of EphB2 SAM was designed that binds SHIP2. Functional characterization of a mutant EphA2 compromised in SHIP2 binding reveals two previously unrecognized functions of SHIP2 in suppressing ligand-induced activation of EphA2 and in promoting chemotactic cell migration in coordination with the receptor.

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Association and dissociation kinetics of colicin E3 and immunity protein 3: Convergence of theory and experiment

Cited by 27 publications

References 23 publications

Dissection of the high rate constant for the binding of a ribotoxin to the ribosome

Dissection of the high rate constant for the binding of a ribotoxin to the ribosome

Forces Driving Chaperone Action

NMR Structure of a Heterodimeric SAM:SAM Complex: Characterization and Manipulation of EphA2 Binding Reveal New Cellular Functions of SHIP2

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