Intramolecular Communication in Anionic Oxidized Phosphanes through a Chelated Proton

2015 ◽  
Vol 21 (23) ◽  
pp. 8613-8625 ◽  
Author(s):  
A. R. Popescu ◽  
I. Rojo ◽  
F. Teixidor ◽  
R. Sillanpää ◽  
C. Viñas
Keyword(s):  
Intramolecular Communication

Hsp70 Escort Protein: More Than a Regulator of Mitochondrial Hsp70

2018 ◽  
Vol 16 (1) ◽  
pp. 64-73 ◽  
Author(s):  
David O. Nyakundi ◽  
Stephen J. Bentley ◽  
Aileen Boshoff
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Domain ◽  
C Terminus ◽  
Cellular Localisation ◽  
The Matrix ◽  
Mitochondrial Hsp70 ◽  
Cellular Compartments ◽  
Intramolecular Communication ◽  
Self Aggregation ◽  
J Protein

Hsp70 members occupy a central role in proteostasis and are found in different eukaryotic cellular compartments. The mitochondrial Hsp70/J-protein machinery performs multiple functions vital for the proper functioning of the mitochondria, including forming part of the import motor that transports proteins from the cytosol into the matrix and inner membrane, and subsequently folds these proteins in the mitochondria. However, unlike other Hsp70s, mitochondrial Hsp70 (mtHsp70) has the propensity to self-aggregate, accumulating as insoluble aggregates. The self-aggregation of mtHsp70 is caused by both interdomain and intramolecular communication within the ATPase and linker domains. Since mtHsp70 is unable to fold itself into an active conformation, it requires an Hsp70 escort protein (Hep) to both inhibit self-aggregation and promote the correct folding. Hep1 orthologues are present in the mitochondria of many eukaryotic cells but are absent in prokaryotes. Hep1 proteins are relatively small and contain a highly conserved zinc-finger domain with one tetracysteine motif that is essential for binding zinc ions and maintaining the function and solubility of the protein. The zinc-finger domain lies towards the C-terminus of Hep1 proteins, with very little conservation outside of this domain. Other than maintaining mtHsp70 in a functional state, Hep1 proteins play a variety of other roles in the cell and have been proposed to function as both chaperones and co-chaperones. The cellular localisation and some of the functions are often speculative and are not common to all Hep1 proteins analysed to date.

scholarly journals Proton Controlled Intramolecular Communication in Dinuclear Ruthenium(II) Polypyridine Complexes

2002 ◽  
Vol 41 (11) ◽  
pp. 2871-2878 ◽  
Author(s):  
Cinzia Di Pietro ◽  
Scolastica Serroni ◽  
Sebastiano Campagna ◽  
Maria Teresa Gandolfi ◽  
Roberto Ballardini ◽  
...  
Keyword(s):  
Dinuclear Ruthenium ◽  
Polypyridine Complexes ◽  
Intramolecular Communication

scholarly journals Type I Restriction Systems: Sophisticated Molecular Machines (a Legacy of Bertani and Weigle)

2000 ◽  
Vol 64 (2) ◽  
pp. 412-434 ◽  
Author(s):  
Noreen E. Murray
Keyword(s):  
Genetic Manipulation ◽  
Molecular Motor ◽  
Restriction Enzymes ◽  
Target Sequence ◽  
Type I ◽  
Dna Translocation ◽  
Chromosomal Dna ◽  
Dna Breakage ◽  
Intramolecular Communication ◽  
Alternative Activities

SUMMARY Restriction enzymes are well known as reagents widely used by molecular biologists for genetic manipulation and analysis, but these reagents represent only one class (type II) of a wider range of enzymes that recognize specific nucleotide sequences in DNA molecules and detect the provenance of the DNA on the basis of specific modifications to their target sequence. Type I restriction and modification (R-M) systems are complex; a single multifunctional enzyme can respond to the modification state of its target sequence with the alternative activities of modification or restriction. In the absence of DNA modification, a type I R-M enzyme behaves like a molecular motor, translocating vast stretches of DNA towards itself before eventually breaking the DNA molecule. These sophisticated enzymes are the focus of this review, which will emphasize those aspects that give insights into more general problems of molecular and microbial biology. Current molecular experiments explore target recognition, intramolecular communication, and enzyme activities, including DNA translocation. Type I R-M systems are notable for their ability to evolve new specificities, even in laboratory cultures. This observation raises the important question of how bacteria protect their chromosomes from destruction by newly acquired restriction specifities. Recent experiments demonstrate proteolytic mechanisms by which cells avoid DNA breakage by a type I R-M system whenever their chromosomal DNA acquires unmodified target sequences. Finally, the review will reflect the present impact of genomic sequences on a field that has previously derived information almost exclusively from the analysis of bacteria commonly studied in the laboratory.

Mechanisms of Inter- and Intramolecular Communication in GPCRs and G Proteins

2008 ◽  
Vol 130 (13) ◽  
pp. 4310-4325 ◽  
Author(s):  
Francesco Raimondi ◽  
Michele Seeber ◽  
Pier G. De Benedetti ◽  
Francesca Fanelli
Keyword(s):  
G Proteins ◽  
Intramolecular Communication

scholarly journals Intramolecular Communication and Allosteric Sites in Enzymes Unraveled by Time-Dependent Linear Response Theory

2019 ◽  
Author(s):  
Bang-Chieh Huang ◽  
Chi-Hong Chang-Chein ◽  
Lee-Wei Yang
Keyword(s):  
Equilibrium State ◽  
Linear Response ◽  
Signal Propagation ◽  
Linear Response Theory ◽  
Time Dependent ◽  
Response Theory ◽  
Functional Sites ◽  
Allosteric Sites ◽  
Intramolecular Communication ◽  
Non Equilibrium

ABSTRACTIt has been an established idea in recent years that protein is a physiochemically connected network. Allostery, understood in this new context, is a manifestation of residue communicating between remote sites in this network, and hence a rising interest to identify functionally relevant communication pathways and the frequent communicators within. Previous studies rationalized the coupling between functional sites and experimentally observed allosteric sites by theoretically discovered high positional/velocity/thermal correlations between these sites. However, for one to systematically discover previously unobserved allosteric sites in any receptor/enzyme providing the position of functional (orthosteric) sites, these high correlations may not be able to identify remote allosteric sites because of a number of false-positives while many of those are located in proximity to the functional site. Also, whether allosteric sites should be found in equilibrium or non-equilibrium state of a protein to be more biologically relevant is not clear, neither is the directionality preference of aforementioned propagating signals. In this study, we devised a time-dependent linear response theory (td-LRT) integrating intrinsic protein dynamics and perturbation forces that excite protein’s temporary reconfiguration at the non-equilibrium state, to describe atom-specific time responses as the propagating mechanical signals and discover that the most frequent remote communicators can be important allosteric sites, mutation of which would deteriorate the hydride transfer rate in DHFR by 2 to 3 orders. The preferred directionality of the signal propagation can be inferred from the asymmetric connection matrix (CM), where the coupling strength between a pair of residues is suggested by their communication score (CS) in the CM, which is found consistent with experimentally characterized nonadditivity of double mutants. Also, the intramolecular communication centers (ICCs), having high CSs, are found evolutionarily conserved, suggesting their biological importance.

scholarly journals BRAF inhibitors promote intermediate BRAF(V600E) conformations and binary interactions with activated RAS

2019 ◽  
Vol 5 (8) ◽  
pp. eaav8463 ◽  
Author(s):  
Ruth Röck ◽  
Johanna E. Mayrhofer ◽  
Omar Torres-Quesada ◽  
Florian Enzler ◽  
Andrea Raffeiner ◽  
...  
Keyword(s):  
Resistance Mechanisms ◽  
Tumor Formation ◽  
Braf V600e ◽  
Braf Inhibitors ◽  
Braf Mutations ◽  
Drug Induced ◽  
Kinase Activation ◽  
Binding Domains ◽  
Intramolecular Communication ◽  
Sequential Formation

Oncogenic BRAF mutations initiate tumor formation by unleashing the autoinhibited kinase conformation and promoting RAS-decoupled proliferative RAF-MEK-ERK signaling. We have engineered luciferase-based biosensors to systematically track full-length BRAF conformations and interactions affected by tumorigenic kinase mutations and GTP loading of RAS. Binding of structurally diverse αC-helix-OUT BRAF inhibitors (BRAFi) showed differences in specificity and efficacy by shifting patient mutation–containing BRAF reporters from the definitive opened to more closed conformations. Unexpectedly, BRAFi engagement with the catalytic pocket of V600E-mutated BRAF stabilized an intermediate and inactive kinase conformation that enhanced binary RAS:RAF interactions, also independently of RAF dimerization in melanoma cells. We present evidence that the interference with RAS interactions and nanoclustering antagonizes the sequential formation of drug-induced RAS:RAF tetramers. This suggests a previously unappreciated allosteric effect of anticancer drug-driven intramolecular communication between the kinase and RAS-binding domains of mutated BRAF, which may further promote paradoxical kinase activation and drug resistance mechanisms.

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