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Cooperativity

About: Cooperativity is a research topic. Over the lifetime, 7027 publications have been published within this topic receiving 258930 citations. The topic is also known as: cooperativity.


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Journal ArticleDOI
TL;DR: The studies establish that C2 domains can serve as independently folding Ca2+/phospholipid-binding domains and support a role for this protein in mediating the Ca2- signal in neurotransmitter release.

470 citations

Journal ArticleDOI
TL;DR: It is shown that an interaction between NF‐kappa B and Sp1 is required for inducible HIV‐1 gene expression and may serve as a regulatory mechanism to activate specific viral and cellular genes.
Abstract: The human immunodeficiency virus (HIV-1) long terminal repeat (LTR) contains two binding sites for NF-kappa B in close proximity to three binding sites for the constitutive transcription factor, Sp1. Previously, stimulation of the HIV enhancer in response to mitogens has been attributed to the binding of NF-kappa B to the viral enhancer. In this report, we show that the binding of NF-kappa B is not by itself sufficient to induce HIV gene expression. Instead, a protein-protein interaction must occur between NF-kappa B and Sp1 bound to an adjacent site. Cooperativity both in DNA binding and in transcriptional activation of NF-kappa B and Sp1 was confirmed by electrophoretic mobility shift gel analysis, DNase footprinting, chemical cross-linking and transfection studies in vivo. With a heterologous promoter, we find that the interaction of NF-kappa B with Sp1 is dependent on orientation and position, and is not observed with other elements, including GATA, CCAAT or octamer. An increase in the spacing between the kappa B and Sp1 elements virtually abolishes this functional interaction, which is not restored when these sites are brought back into the same helical position. Several other promoters regulated by NF-kappa B also contain kappa B in proximity to Sp1 binding sites. These findings suggest that an interaction between NF-kappa B and Sp1 is required for inducible HIV-1 gene expression and may serve as a regulatory mechanism to activate specific viral and cellular genes.

464 citations

Journal ArticleDOI
TL;DR: The "HZ" (hydrophobic zipper) hypothesis shows how proteins could find globally optimal states without exhaustive search.
Abstract: How does a protein find its native state without a globally exhaustive search? We propose the "HZ" (hydrophobic zipper) hypothesis: hydrophobic contacts act as constraints that bring other contacts into spatial proximity, which then further constrain and zip up the next contacts, etc. In contrast to helix-coil cooperativity, HZ-heteropolymer collapse cooperativity is driven by nonlocal interactions, causes sheet and irregular conformations in addition to helices, leads to secondary structures concurrently with early hydrophobic core formation, is much more sequence dependent than helix-coil processes, and involves compact intermediate states that have much secondary--but little tertiary--structure. Hydrophobic contacts in the 1992 Protein Data Bank have the type of "topological localness" predicted by the hypothesis. The HZ paths for amino acid sequences that mimic crambin and bovine pancreatic trypsin inhibitor are quickly found by computer; the best configurations thus reached have single hydrophobic cores that are within about 3 kcal/mol of the global minimum. This hypothesis shows how proteins could find globally optimal states without exhaustive search.

461 citations

Journal ArticleDOI
TL;DR: It is observed that at room temperature a fast exchange on the second time scale exists between molecules and stacks of sergeant (R)-1 and soldier 2, and that interconversion between M and P helices is fast at this temperature.
Abstract: On the basis of temperature-dependent UV-vis and circular dichroism (CD) spectroscopy measurements, we observed that C3-symmetrical discotic molecules, chiral (R)-1 and achiral 2, both self-assemble in a highly cooperative fashion. Chiral (R)-1 shows a higher degree of cooperativity, meaning it requires a larger nucleus before elongation sets in, as compared to achiral 2. Next to that, we investigated the mechanism of the "sergeants-and-soldiers" principle, where we found that the chiral sergeant (R)-1 strongly amplifies the preference in handedness of the mixed stacks of (R)-1 and 2. However, the elongation temperature and the degree of cooperativity are linearly dependent on both, at least in the regime above 4% of sergeant in the mixed system. Remarkably, we observed that at room temperature a fast exchange on the second time scale exists between molecules and stacks of sergeant (R)-1 and soldier 2, and that interconversion between M and P helices is fast at this temperature.

446 citations

Journal ArticleDOI
TL;DR: The shape of the funnel bottom, which depicts the stability of the native state ensemble, also accounts for the thermodynamic parameters of activation that characterize these extremophilic enzymes, therefore providing a rational basis for stability-activity relationships in protein adaptation to extreme temperatures.

441 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023202
2022350
2021180
2020195
2019191
2018186