Related Experiment Video
Updated: Jun 2, 2025
07:15
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
10.9K
Molecular Determinants of Protein Pathogenicity at the Single-Aggregate Level
Agnieszka Urbanek1,2, Emma F Garland1,2, Emily E Prescott1,2
1Sheffield Institute for Translational Neuroscience, Division of Neuroscience, University of Sheffield, Sheffield, S10 2HQ, UK.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 13, 2025
Summary
Understanding protein aggregates is key to diseases like Alzheimer's and Parkinson's. This study reveals how aggregate variations impact biological functions, offering new insights into health and disease at the single-aggregate level.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Biology
Background:
- Protein aggregates exhibit significant heterogeneity in size, structure, and composition.
- Understanding structure-function relationships in protein aggregates is crucial for cellular homeostasis.
- Dysfunctional protein aggregation is implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's.
Purpose of the Study:
- To investigate how variations in protein aggregate features influence biological functions.
- To explore the impact of size, composition, post-translational modifications, and mutations on aggregate function.
- To uncover novel disease-relevant pathways associated with protein aggregation.
Main Methods:
- A bottom-up approach was employed to analyze protein aggregates.
- The study focused on variations in aggregate composition and morphology.
- Methods were applied to Alzheimer's and Parkinson's associated proteins.
Main Results:
- Subtle alterations in protein aggregate composition and morphology can shift cellular states between healthy and pathological conditions.
- Novel disease-relevant pathways were identified through the analysis of Alzheimer's and Parkinson's associated proteins.
- The study provides insights into the molecular basis of protein functions at the single-aggregate level.
Conclusions:
- The study enhances understanding of protein aggregate roles in both health and disease.
- Findings highlight the profound influence of aggregate heterogeneity on biological functions.
- This research offers a foundation for further investigation into proteinopathies.
Keywords:
neurodegenerative diseaseprotein aggregationsingle‐molecule imagingstructure‐function relationshipMore Related Videos
Related Concept Videos
02:41Protein Complex Assembly
10.5K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.5K
01:57Protein Complexes with Interchangeable Parts
2.5K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.5K
03:03Amyloid Fibrils
9.2K
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,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.2K
01:22Protein Folding
117.2K
Overview
117.2K
02:28Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
02:04Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K