Related Experiment Video
Updated: Jun 3, 2026
10:56
Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
Intrinsically disordered proteins may escape unwanted interactions via functional misfolding
1Department of Molecular Medicine, University of South Florida, Tampa, FL, USA. vuversky@health.usf.edu
Biochimica Et Biophysica Acta
|March 29, 2011
Summary
Intrinsically disordered proteins (IDPs) are vital in cells. A new concept, functional misfolding, suggests IDPs may misfold to shield interaction sites, preventing unwanted cellular binding.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Intrinsically disordered proteins (IDPs) are abundant and crucial for cellular functions.
- IDPs engage in diverse intermolecular interactions, often exhibiting binding promiscuity.
- While lacking stable structures, IDPs can adopt specific conformations upon partner binding.
Purpose of the Study:
- To explore the mechanisms preventing intrinsically disordered proteins from non-specific interactions.
- To introduce and discuss the concept of functional misfolding in IDPs.
- To understand how IDPs manage their interaction propensity.
Main Methods:
- Review of existing literature on intrinsically disordered protein conformational behavior.
- Analysis of data on the fine structure and dynamics of selected IDPs.
- Conceptual framework development based on accumulated evidence.
Main Results:
- IDPs possess transient, preformed secondary structure elements prone to interaction.
- Functional misfolding is proposed as a mechanism to sequester these interaction elements.
- Intramolecular interactions may form a protective cage, preventing non-native binding.
Conclusions:
- Functional misfolding offers a potential explanation for the specificity of IDP interactions.
- IDPs may utilize intramolecular misfolding to regulate their binding capabilities.
- This mechanism ensures IDPs interact with native partners while avoiding off-target associations.
Related Concept Videos
02:18Intrinsically Disordered Proteins
Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
02:18Intrinsically Disordered Proteins
Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
03:00Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
03:00Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:25Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...