scholarly journals Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA

2017 ◽  
Vol 474 (18) ◽  
pp. 3121-3135 ◽  
Author(s):  
Eva I. Hyde ◽  
Philip Callow ◽  
Karthik V. Rajasekar ◽  
Peter Timmins ◽  
Trushar R. Patel ◽  
...  
Keyword(s):  
Complex Formation ◽  
Transcriptional Repression ◽  
Radius Of Gyration ◽  
Wild Type ◽  
Conformational Restriction ◽  
Intrinsically Disordered ◽  
Disordered Structure ◽  
Binary Complexes ◽  
Dna Partitioning ◽  
Dna Complex

The ParB protein, KorB, from the RK2 plasmid is required for DNA partitioning and transcriptional repression. It acts co-operatively with other proteins, including the repressor KorA. Like many multifunctional proteins, KorB contains regions of intrinsically disordered structure, existing in a large ensemble of interconverting conformations. Using NMR spectroscopy, circular dichroism and small-angle neutron scattering, we studied KorB selectively within its binary complexes with KorA and DNA, and within the ternary KorA/KorB/DNA complex. The bound KorB protein remains disordered with a mobile C-terminal domain and no changes in the secondary structure, but increases in the radius of gyration on complex formation. Comparison of wild-type KorB with an N-terminal deletion mutant allows a model of the ensemble average distances between the domains when bound to DNA. We propose that the positive co-operativity between KorB, KorA and DNA results from conformational restriction of KorB on binding each partner, while maintaining disorder.

scholarly journals 2P117 Thermodynamics of protein-DNA complex formation in relation to structure

2004 ◽  
Vol 44 (supplement) ◽  
pp. S139
Author(s):  
H. Uedaira ◽  
H. Kono ◽  
Ponraj Prabakaran ◽  
K. Kitajima ◽  
A. Sarai
Keyword(s):  
Complex Formation ◽  
Dna Complex

scholarly journals Deciphering the Role of Residues Involved in Disorder-To-Order Transition Regions in Archaeal tRNA Methyltransferase 5

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 399
Author(s):  
Ambuj Srivastava ◽  
Dhanusha Yesudhas ◽  
Shandar Ahmad ◽  
M. Michael Gromiha
Keyword(s):  
Three Dimensional ◽  
Md Simulations ◽  
Order Transition ◽  
Free Form ◽  
Wild Type ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Type Complex ◽  
In The Wild ◽  
Trna Methyltransferase

tRNA methyltransferase 5 (Trm5) enzyme is an S-adenosyl methionine (AdoMet)-dependent methyltransferase which methylates the G37 nucleotide at the N1 atom of the tRNA. The free form of Trm5 enzyme has three intrinsically disordered regions, which are highly flexible and lack stable three-dimensional structures. These regions gain ordered structures upon the complex formation with tRNA, also called disorder-to-order transition (DOT) regions. In this study, we performed molecular dynamics (MD) simulations of archaeal Trm5 in free and complex forms and observed that the DOT residues are highly flexible in free proteins and become stable in complex structures. The energetic contributions show that DOT residues are important for stabilising the complex. The DOT1 and DOT2 are mainly observed to be important for stabilising the complex, while DOT3 is present near the active site to coordinate the interactions between methyl-donating ligands and G37 nucleotides. In addition, mutational studies on the Trm5 complex showed that the wild type is more stable than the G37A tRNA mutant complex. The loss of productive interactions upon G37A mutation drives the AdoMet ligand away from the 37th nucleotide, and Arg145 in DOT3 plays a crucial role in stabilising the ligand, as well as the G37 nucleotide, in the wild-type complex. Further, the overall energetic contribution calculated using MMPBSA corroborates that the wild-type complex has a better affinity between Trm5 and tRNA. Overall, our study reveals that targeting DOT regions for binding could improve the inhibition of Trm5.

scholarly journals Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a

1999 ◽  
Vol 13 (19) ◽  
pp. 2490-2501 ◽  
Author(s):  
M. Murphy ◽  
J. Ahn ◽  
K. K. Walker ◽  
W. H. Hoffman ◽  
R. M. Evans ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Wild Type ◽  
Wild Type P53

scholarly journals DNA tumor virus oncoproteins and retinoblastoma gene mutations share the ability to relieve the cell's requirement for cyclin D1 function in G1.

1994 ◽  
Vol 125 (3) ◽  
pp. 625-638 ◽  
Author(s):  
J Lukas ◽  
H Müller ◽  
J Bartkova ◽  
D Spitkovsky ◽  
A A Kjerulff ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Complex Formation ◽  
Cyclin D1 ◽  
Cell Lines ◽  
T Antigen ◽  
Regulatory Function ◽  
Retinoblastoma Gene ◽  
Checkpoint Control ◽  
Wild Type ◽  
In Cells

The retinoblastoma gene product (pRB) participates in the regulation of the cell division cycle through complex formation with numerous cellular regulatory proteins including the potentially oncogenic cyclin D1. Extending the current view of the emerging functional interplay between pRB and D-type cyclins, we now report that cyclin D1 expression is positively regulated by pRB. Cyclin D1 mRNA and protein is specifically downregulated in cells expressing SV40 large T antigen, adenovirus E1A, and papillomavirus E7/E6 oncogene products and this effect requires intact RB-binding, CR2 domain of E1A. Exceptionally low expression of cyclin D1 is also seen in genetically RB-deficient cell lines, in which ectopically expressed wild-type pRB results in specific induction of this G1 cyclin. At the functional level, antibody-mediated cyclin D1 knockout experiments demonstrate that the cyclin D1 protein, normally required for G1 progression, is dispensable for passage through the cell cycle in cell lines whose pRB is inactivated through complex formation with T antigen, E1A, or E7 oncoproteins as well as in cells which have suffered loss-of-function mutations of the RB gene. The requirement for cyclin D1 function is not regained upon experimental elevation of cyclin D1 expression in cells with mutant RB, while reintroduction of wild-type RB into RB-deficient cells leads to restoration of the cyclin D1 checkpoint. These results strongly suggest that pRB serves as a major target of cyclin D1 whose cell cycle regulatory function becomes dispensable in cells lacking functional RB. Based on available data including this study, we propose a model for an autoregulatory feedback loop mechanism that regulates both the expression of the cyclin D1 gene and the activity of pRB, thereby contributing to a G1 phase checkpoint control in cycling mammalian cells.

scholarly journals Transcriptional repression ofAurora-Agene by wild-type p53 through directly binding to its promoter with histone deacetylase 1 and mSin3a

2017 ◽  
Vol 142 (1) ◽  
pp. 92-108
Author(s):  
Tsung-Ying Yang ◽  
Chieh-Lin Jerry Teng ◽  
Tsung-Chieh Chester Lin ◽  
Kun-Chieh Chen ◽  
Shih-Lan Hsu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Wild Type ◽  
Histone Deacetylase 1 ◽  
Wild Type P53

scholarly journals Intrinsically disordered caldesmon binds calmodulin via the “buttons on a string” mechanism

PeerJ ◽  
2015 ◽  
Vol 3 ◽  
pp. e1265 ◽  
Author(s):  
Sergei E. Permyakov ◽  
Eugene A. Permyakov ◽  
Vladimir N. Uversky
Keyword(s):  
Local Structure ◽  
Intrinsically Disordered Proteins ◽  
String Model ◽  
Electrostatic Attraction ◽  
Disordered Proteins ◽  
Wild Type ◽  
Intrinsically Disordered ◽  
Tryptophan Residues ◽  
Specific Packing ◽  
Oppositely Charged

We show here that chicken gizzard caldesmon (CaD) and its C-terminal domain (residues 636–771, CaD136) are intrinsically disordered proteins. The computational and experimental analyses of the wild type CaD136and series of its single tryptophan mutants (W674A, W707A, and W737A) and a double tryptophan mutant (W674A/W707A) suggested that although the interaction of CaD136with calmodulin (CaM) can be driven by the non-specific electrostatic attraction between these oppositely charged molecules, the specificity of CaD136-CaM binding is likely to be determined by the specific packing of important CaD136tryptophan residues at the CaD136-CaM interface. It is suggested that this interaction can be described as the “buttons on a charged string” model, where the electrostatic attraction between the intrinsically disordered CaD136and the CaM is solidified in a “snapping buttons” manner by specific packing of the CaD136“pliable buttons” (which are the short segments of fluctuating local structure condensed around the tryptophan residues) at the CaD136-CaM interface. Our data also show that all three “buttons” are important for binding, since mutation of any of the tryptophans affects CaD136-CaM binding and since CaD136remains CaM-buttoned even when two of the three tryptophans are mutated to alanines.

scholarly journals WT and A53T α-synuclein systems: Melting Diagram and its new interpretation

2019 ◽  
Author(s):  
M. Bokor ◽  
Á. Tantos ◽  
P. Tompa ◽  
K.-H. Han ◽  
K. Tompa
Keyword(s):  
Secondary Structure ◽  
Structural Disorder ◽  
Water Molecules ◽  
Hydration Water ◽  
Wild Type ◽  
Water Binding ◽  
Potential Barriers ◽  
Intrinsically Disordered ◽  
Mobile Water ◽  
Binding Interfaces

AbstractParkinson’s disease is connected with abnormal α-synuclein (αS) aggregation. Energetics of potential barriers governing motions of hydration water is examined. Information about the distributions and heights of potential barriers is gained by a thermodynamical approach. The ratios of the heterogeneous water-binding interfaces measure proteins’ structural disorder. All αS forms possess secondary structural elements though they are intrinsically disordered. Monomers are functional at the lowest potential barriers, where mobile hydration water exists, with monolayer coverage of mobile hydration. The αS monomer contains 33% secondary structure and is more compact than a random coil. A53T αS monomer has a more open structure than the wild type. Monomers realize all possible hydrogen bonds. Half of the mobile hydration water amount for monomers is missing in αS oligomers and αS amyloids. Oligomers are ordered by 66%. Mobile water molecules in the first hydration shell of amyloids are the weakest bound compared to other forms. Wild type and A53T amyloids show identical, low-level hydration, and are considered as disordered to 75%.Statement of SignificanceAggregation of α-synuclein into oligomers, amyloid fibrils is a hallmark of Parkinson’s disease. A thermodynamic approach provides information on the heterogeneity of protein-water bonds in the wild type and A53T mutant monomers, oligomers, amyloids. This information can be related to ratios of heterogeneous water-binding interfaces, which measure the proteins’ structural disorder. Both α-synuclein monomers are intrinsically disordered. The monomers nevertheless have 33% secondary structure. They are functional as long as mobile water molecules surround them. They realize every possible H-bonds with water. Oligomers are like globular proteins with 66% ordered structure. Amyloids are disordered to 75% and are poorly hydrated with loosely bound water. Their hydration is identical. Oligomers, amyloids have only half as much hydrating mobile water as monomers.

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