Electrostatic aspects of protein–protein interactions

Sheinerman, Felix B.; Norel, Raquel; Honig, Barry

doi:10.1016/s0959-440x(00)00065-8

Cited by 692 publications

(518 citation statements)

References 59 publications

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“…We therefore concluded that the mutations are not sufficient to disrupt the intramolecular interactions in the full-length protein and secondly, that these residues are not directly involved in signaling. Electrostatic forces have been shown to accelerate the initial binding steps in the formation of protein complexes (Sheinerman et al, 2000;Godderz et al, 2003;Ivanova and Lu, 2008), and the complementarycharged residues we predict to be located at the edge of the ARC2 and LRR interface could be envisioned to play such a role in the interdomain interactions of the CC-NB-ARC and LRR. After the elicitor-mediated dissociation of the CC-NB-ARC and LRR domains, as shown in this study, a fast reassociation is expected to take place that enables the NB-LRR protein to be activated multiple times (Rairdan and Moffett, 2006).…”

Section: Discussionmentioning

confidence: 83%

Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa2

et al. 2013

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Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins.Resistance (R) proteins play a central role in the recognition-based immune system of plants. Unlike vertebrates, plants lack an adaptive immune system with highly specialized immune cells. Instead, they rely on an innate immune system in which each cell is autonomous. Two types of immune receptors can be distinguished in plants, pathogen-associated molecular patterns recognition receptors that detect conserved molecular patterns in plant pathogens and intracellular R proteins that recognize specific effectors employed by pathogens as modifiers of host metabolism or defense mechanisms (Jones and Dangl, 2006). Effector-triggered activation of R proteins leads to an array of protective responses, often culminating in programmed cell death at the site of infection (Greenberg and Yao, 2004), thereby preventing further ingress of the pathogen. Pathogens have evolved mechanisms to evade recognition by R proteins and to regain their virulence (Dodds and Rathjen, 2010). This continuous coevolutionary process between host and pathogen has resulted in a reservoir of highly diverse R proteins in plants, enabling them to counteract a wide range of pathogens and pests.The most common class of R proteins consists of nucleotide-binding (NB)-leucine-rich repeat (LRR) proteins with a tripartite domain architecture, which roughly corresponds to an N-terminal response domain (a coiled coil [CC] or Toll/Interleukin-1 receptor [TIR] domain) involved in downstream signaling, a central molecula...

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Section: Discussionmentioning

confidence: 83%

Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa2

et al. 2013

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“…protein binding ͉ transient nonspecific encounter complexes ͉ paramagnetic relaxation enhancement ͉ bacterial phosphotransferase system E xperimental and theoretical studies have provided evidence that transient nonspecific encounter complexes play an important role in protein binding and function (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The formation of weakly bound nonspecific complexes, often dominated by long-range electrostatic interactions, enhances the on-rate of binding by increasing the interaction cross-section and reducing the conformational space to be searched on the path to the specific complex.…”

Section: Recent Paramagnetic Relaxation Enhancement (Pre) Studies On mentioning

confidence: 99%

Replica exchange simulations of transient encounter complexes in protein–protein association

Kim

Tang

Clore

et al. 2008

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

110

145

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Recent paramagnetic relaxation enhancement (PRE) studies on several weakly interacting protein complexes have unequivocally demonstrated the existence of transient encounter complexes. Here, we present a computational method to study proteinprotein binding by creating equilibrium ensembles that include both specific and nonspecific protein complexes. In a joint analysis of simulation and experiment we explore the physical nature and underlying physicochemical characteristics of encounter complexes involving three protein-protein interactions of the bacterial phosphotransferase system. Replica exchange Monte Carlo simulations using a coarse-grained energy function recover the structures of the specific complexes and produce binding affinities in good agreement with experiment. Together with the specific complex, a relatively small number of distinct nonspecific complexes largely accounts for the measured PRE data. The combined relative population of the latter is less than ϳ10%. The binding interfaces of the specific and nonspecific complexes differ primarily in size but exhibit similar amino acid compositions. We find that the overall funnel-shaped energy landscape of complex formation is dominated by the specific complex, a small number of structured nonspecific complexes, and a diffuse cloud of loosely bound complexes connecting the specific and nonspecific binding sites with each other and the unbound state. Nonspecific complexes may not only accelerate the binding kinetics by enhancing the rate of success of random diffusional encounters but also play a role in protein function as alternative binding modes.protein binding ͉ transient nonspecific encounter complexes ͉ paramagnetic relaxation enhancement ͉ bacterial phosphotransferase system E xperimental and theoretical studies have provided evidence that transient nonspecific encounter complexes play an important role in protein binding and function (1-17). The formation of weakly bound nonspecific complexes, often dominated by long-range electrostatic interactions, enhances the on-rate of binding by increasing the interaction cross-section and reducing the conformational space to be searched on the path to the specific complex. From the thermodynamic standpoint, weak nonspecific complexes contribute to the overall affinity by bolstering contacts between proteins or domains (14,17,18). Despite the importance of encounter complexes, little is known about their relative populations or structures, largely because of their transient nature.Recent work has shown that paramagnetic relaxation enhancement (PRE) provides a very sensitive tool for detecting the presence of low population transient species in solution. PRE measurements have unequivocally demonstrated the existence of transient encounter complexes in protein-DNA (19, 20) and protein-protein (4-8, 21) interactions. These experiments rely on three key observations: (i) the observed intermolecular PRE relaxation rates in the fast-exchange regime are population averages of all complexes present in solution;...

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“…Electrostatic interactions also play an important role in determining thermodynamics of binding; i.e., binding affinity (Novotny and Sharp, 1992;Fersht, 1993, 1995;Zhu and Karlin, 1996;Chong et al, 1998;Sheinerman et al, 2000;Norel et al, 2001;Rauch et al, 2002). Substrate binding allows the formation of (potentially) favorable charge-charge interactions between the substrate and target, as well as stabilizing specific salt-bridges and hydrogen bonds Fersht, 1993, 1995;Chong et al, 1998).…”

Section: Iib Biomolecule-ligand and -Biomolecule Interactionsmentioning

confidence: 99%

Computational Methods for Biomolecular Electrostatics

Dong

Olsen

Baker

2008

Methods in Cell Biology

116

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An understanding of intermolecular interactions is essential for insight into how cells develop, operate, communicate and control their activities. Such interactions include several components: contributions from linear, angular, and torsional forces in covalent bonds, van der Waals forces, as well as electrostatics. Among the various components of molecular interactions, electrostatics are of special importance because of their long range and their influence on polar or charged molecules, including water, aqueous ions, and amino or nucleic acids, which are some of the primary components of living systems. Electrostatics, therefore, play important roles in determining the structure, motion and function of a wide range of biological molecules. This chapter presents a brief overview of electrostatic interactions in cellular systems with a particular focus on how computational tools can be used to investigate these types of interactions.

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Electrostatic aspects of protein–protein interactions

Cited by 692 publications

References 59 publications

Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa2

Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa2

Replica exchange simulations of transient encounter complexes in protein–protein association

Computational Methods for Biomolecular Electrostatics

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