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Conserved Binding Sites

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

Conserved Binding Sites

Conserved Binding Sites

Cooperative Binding of Transcription Regulators

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...

Ligand Binding Sites

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

Cooperative Allosteric Transitions

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...

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Related Experiment Video

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Identification of consensus binding sites clarifies FMRP binding determinants.

Bart R Anderson¹, Pankaj Chopra², Joshua A Suhl³

¹Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.

Nucleic Acids Research

|July 6, 2016

Summary

Fragile X mental retardation protein (FMRP) binding to messenger RNAs (mRNAs) was clarified using a consensus binding sequence dataset. This study identified key sequence motifs and binding regions, advancing understanding of FMRP

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Area of Science:

Neuroscience
Molecular Biology
Genetics

Background:

Fragile X mental retardation protein (FMRP) is vital for neuronal development and function.
Previous research on FMRP target mRNA selection and binding motifs yielded inconsistent results.
A clear understanding of FMRP's RNA binding determinants has been lacking.

Purpose of the Study:

To clarify the binding determinants of FMRP to its target mRNAs.
To establish a reproducible dataset of FMRP consensus binding sequences (FCBS).
To identify sequence and structural motifs governing FMRP-RNA interactions.

Main Methods:

Comparative analysis of two published FMRP CLIP sequencing datasets.
Generation of a shared dataset of reproducibly identified FMRP consensus binding sequences (FCBS).
Bioinformatic analysis to identify sequence motifs and binding site distribution.

Main Results:

The FCBS dataset corroborated TGGA and GAC motifs and identified a novel TAY motif.
FMRP preferentially binds to the coding regions of target mRNAs.
FMRP also binds to 3' untranslated regions (UTRs) in a subset of target mRNAs.

Conclusions:

The identified motifs (TGGA, GAC, TAY) are key determinants of FMRP binding.
FMRP exhibits preferential binding to coding regions, with additional interactions in 3' UTRs.
The FCBS dataset serves as a valuable resource for studying FMRP targets and functions.