DefinitionThis section has been translated automatically.
Chaperones are proteins that "help" newly synthesized proteins to fold correctly. The term "chaperones" was chosen "because they protect immature proteins from harmful configurations". Chaperones represent an extremely heterogeneous (unrelated to each other) functionally related protein complex, which is only characterised by their functional commonality, i.e. protein folding (Brandvold KR et al. 2015). Their members were formed at very different times in evolution.
Newly synthesized proteins organize themselves in their specific, native, functional conformation. This is basically the primary structure, the sequence of amino acids. Smaller proteins can spontaneously fold in the right way (a classic example of spontaneous folding is ribonuclease). Larger, complex, unfolded proteins require "aids" for correct folding.
Unfolded proteins have highly reactive hydrophobic side chains. These can combine with other hydrophobic molecules or other protein chains to form completely disordered protein aggregates. Such protein aggregates lose their biological function and represent useless or cell-damaging protein waste. To avoid this process, which is unphysiological for the cell, the cell uses a complex, highly conserved protein machinery, the chaperones ("molecular Red Cross").
Chaperones prevent the aggregation of incompletely folded protein chains by shielding the exposed hydrophobic amino acid segments. After successful, chaperone-assisted folding, these hydrophobic segments are hidden inside the protein. Chaperones are then only active until the folded, native state of the protein is reached. In this way, chaperones can differentiate precisely between unfolded and folded proteins. Chaperones act as a catalyst, assisting in the correct folding of the proteins without becoming part of the structure themselves.
Some chaperones exhibit an increased synthesis rate at unphysiologically high temperatures. They therefore belong to the classical heat shock proteins.
ClassificationThis section has been translated automatically.
Chaperonins are a subgroup of the molecular chaperones. In eukaryotes, these are located exclusively in the mitochondria. Mutations in the HSPD1 gene coding for chaperonins are responsible for hereditary forms of spastic spinal paralysis and leukodystrophy.
Chaperonins form large, cylindrical complexes about 14 nm wide and 15-16 nm high (structure comparable to a donate). In their cavities they assist the folding of proteins. Chaperonins are constitutively expressed, for example in stress situations of the cell, e.g. at elevated temperature (heat shock proteins).
Note(s)This section has been translated automatically.
Chaperones have medical relevance in diseases in which misfolded proteins and their accumulation lead to cell damage. Creutzfeldt-Jakob disease (CJD), Alzheimer's disease and various forms of cutaneous and systemic amyloidosis are important examples of "protein misfolding".
LiteratureThis section has been translated automatically.
- Alberts B et al. (2004) Molecular biology of the cell. Weinheim: Wiley-VCH.
- Brandvold KR et al.(2015) The Chemical Biology of Molecular Chaperones--Implications for Modulation of Proteostasis. J Mol Biol 427:2931-2347.
- Huth E (2005) Cellular uptake and intracellular fate of particulate drug delivery systems. Inaugural dissertation for the degree of doctor of the faculty of chemistry, pharmacy and geosciences of the Albert-Ludwigs-University Freiburg.
- Kim YE et al.(2013) Molecular chaperonefunctions in protein folding and proteostasis. Annu Rev Biochem 82:323-355.
- Smith HL et al (2015) Molecular chaperones and neuronal proteostasis. Semin Cell Dev Biol 40:142-152.
- Sumera A et al (2015) Review: beta-thalassemia and molecular chaperones. Blood Cells Mol Dis 54:348-352.
- Taldone T et al. (2014) Protein chaperones: a composition of matter review (2008 - 2013). Expert Opin Ther Pat 24:501-518.
- S.a. Video of the Max Planck Institute