Lecture

Protein Quality Control of Membraneless Organelles

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Description

This lecture explores the protein quality control mechanisms of membraneless organelles, focusing on the implications for stress responses and age-related diseases. It covers the formation of membraneless organelles through liquid-liquid phase separation, the role of multivalent proteins and disordered proteins, and the conversion of proteins into amyloid-like deposits. The lecture also discusses the impact of disease-linked mutations on the maturation of liquid droplets. Furthermore, it delves into the cellular protein quality control system, the role of chaperones, and the clearance of misfolded proteins. The consequences of protein mishandling, the formation of stress granules, and the interplay between nucleoli functionality and protein aggregation are also addressed.

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Related concepts (32)

Protein aggregation

In molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate (i.e., accumulate and clump together) either intra- or extracellularly. Protein aggregates have been implicated in a wide variety of diseases known as amyloidoses, including ALS, Alzheimer's, Parkinson's and prion disease. After synthesis, proteins typically fold into a particular three-dimensional conformation that is the most thermodynamically favorable: their native state.

Chaperone (protein)

In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis. The first molecular chaperones discovered were a type of assembly chaperones which assist in the assembly of nucleosomes from folded histones and DNA.

Protein folding

Protein folding is the physical process where a protein chain is translated into its native three-dimensional structure, typically a "folded" conformation, by which the protein becomes biologically functional. Via an expeditious and reproducible process, a polypeptide folds into its characteristic three-dimensional structure from a random coil. Each protein exists first as an unfolded polypeptide or random coil after being translated from a sequence of mRNA into a linear chain of amino acids.

Amyloid

Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human body, amyloids have been linked to the development of various diseases. Pathogenic amyloids form when previously healthy proteins lose their normal structure and physiological functions (misfolding) and form fibrous deposits within and around cells.

Amyloid beta

Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms.

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