Theoretical models for cooperative binding—I. one-site creator of binding sites

Chapter 3 provides a brief overview of allostery, the modulation of protein activity that is caused by an indirect interaction between structurally remote binding sites. In this mode of intramolecular regulatory control, the binding of ligand at a protein’s active site is influenced by the binding of another ligand at a different site in the same protein. This interaction at a distance is mediated by a ligation-induced transition between alternative conformational states. Hemoglobin is regarded as the “allosteric paradigm,” and the oxygenation-linked transition between alternative quaternary conformations provides a textbook example of how allostery works. This chapter reviews different theoretical models, such as the Monod-Wyman-Changeux “two-state” model, to explain the allosteric regulation of hemoglobin function.

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Bimodality in the cooperative binding of ligands to molecules with multiple binding sites

The Journal of Physical Chemistry ◽

10.1021/j100302a033 ◽

1987 ◽

Vol 91 (18) ◽

pp. 4813-4820 ◽

Cited By ~ 15

Author(s):

Johannes. Reiter ◽

Irving R. Epstein

Keyword(s):

Binding Sites ◽

Cooperative Binding ◽

Multiple Binding Sites ◽

Multiple Binding

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Interleukin-2 (IL-2) Regulates the Accessibility of the IL-2-Responsive Enhancer in the IL-2 Receptor α Gene to Transcription Factors

Molecular and Cellular Biology ◽

10.1128/mcb.19.4.2681 ◽

1999 ◽

Vol 19 (4) ◽

pp. 2681-2689 ◽

Cited By ~ 17

Author(s):

Corinne Rusterholz ◽

Patricia Corthésy Henrioud ◽

Markus Nabholz

Keyword(s):

Transcription Factors ◽

T Lymphocytes ◽

Binding Sites ◽

Interleukin 2 ◽

Binding Activity ◽

Micrococcal Nuclease ◽

Cooperative Binding ◽

Α Subunit ◽

Hypersensitive Sites

ABSTRACT Interleukin-2 (IL-2) responsiveness of T lymphocytes is controlled through transcription of the IL-2 receptor (IL-2R) α subunit by antigen and by IL-2 itself. IL-2 induces IL-2Rα transcription via an IL-2-responsive enhancer (IL-2rE), whose activity depends on the cooperative binding of IL-2-induced STAT5 to two sites and of constitutively active Elf-1 to a third one. Here we describe the changes in IL-2rE chromatin that occur in normal T lymphocytes upon activation of IL-2Rα expression. In cells induced to transiently express IL-2Rα with concanavalin A (which mimics antigen), none of the IL-2rE sites is occupied despite the presence of Elf-1 and STAT1, which bind to the IL-2rE in vitro. The two STAT binding sites are occupied rapidly upon IL-2 stimulation, concomitantly with STAT5 activation. Occupation of the Elf-1 binding site is delayed, although Elf-1 concentration and binding activity are not modified by IL-2. Digestion of T-cell chromatin with DNase I and micrococcal nuclease shows that IL-2 induces the appearance of nuclease-hypersensitive sites flanking the IL-2rE. Thus IL-2, in addition to activating STAT5, appears to regulate IL-2Rα transcription by making IL-2Rα chromatin accessible to transcription factors.

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Mechanisms of modulation of pre-mRNA 3D structural scaffolds for splicing substrate definition

10.1101/2021.12.01.470860 ◽

2021 ◽

Author(s):

Kaushik Saha ◽

Gourisankar Ghosh

Keyword(s):

Splice Site ◽

Binding Sites ◽

Sr Proteins ◽

Cooperative Binding ◽

Large Excess ◽

Sr Protein ◽

Spliceosome Assembly ◽

Splice Signal ◽

Protein Molecules ◽

U1 Snrnp

Coordination of different serine-arginine-rich (SR) proteins - a class of critical splicing activators - facilitates recognition of the highly degenerate cognate splice signal sequences against the background sequences. Yet, the mechanistic details of their actions remain unclear. Here we show that cooperative binding of SR proteins to exonic and intronic motifs remodels the pre-mRNA 3D structural scaffold. The scaffold generated by pre-mRNA-specific combinations of different SR proteins in an appropriate stoichiometry is recognized by U1 snRNP. A large excess of U1 snRNP particles displaces the majority of the bound SR protein molecules from the remodeled pre-mRNA. A higher than optimal stoichiometry of SR proteins occludes the binding sites on the pre-mRNA, raising the U1 snRNP levels required for SR protein displacement and potentially impeding spliceosome assembly. This novel step is important for distinguishing the substrate and the non-substrate by U2AF65 - the primary 3' splice site-recognizing factor. Overall, this work elucidates early regulatory steps of mammalian splicing substrate definition by SR proteins.

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