Use the following passage to answer questions: Under conditions of cell stress, such as exposure to heat, the weak bonds within a protein can be broken, leading to protein misfolding and self-association. When the concentration of misfolded polypeptides becomes high enough, they can form larger aggregates that are very stable because strong bonds occur between the molecules. Many age-related diseases, including Alzheimer's, Parkinson's, and type 2 diabetes, are considered to be the result of protein aggregates, which can eventually cause tissue death. Chaperone molecules bind with high... Show more Use the following passage to answer questions: Under conditions of cell stress, such as exposure to heat, the weak bonds within a protein can be broken, leading to protein misfolding and self-association. When the concentration of misfolded polypeptides becomes high enough, they can form larger aggregates that are very stable because strong bonds occur between the molecules. Many age-related diseases, including Alzheimer's, Parkinson's, and type 2 diabetes, are considered to be the result of protein aggregates, which can eventually cause tissue death. Chaperone molecules bind with high affinity to exposed hydrophobic regions on the surface of misfolded polypeptides and reduce aggregation. However, there is increasing evidence that chaperones do not merely act like sponges that associate with misfolded polypeptides and prevent them from aggregating. Along with a complex of molecules, chaperones can help misfolded substrates unfold and are thus also called unfoldases. Once the substrates are completely unfolded, they can then spontaneously refold into their native conformation. Although chaperones can act on different types of proteins, they unfold them with varying degrees of efficiency. For example, one of the major families of chaperones, which are highly conserved from bacteria to eukaryotes, is called GroEL/GroES. Compared with other chaperones, GroEL/GroES can rapidly convert misfolded rhodanese (rho), a mitochondrial enzyme involved in detoxifying cyanide, into its unfolded form. However, it is unclear in general whether a vast excess of native, properly folded proteins could compete with misfolded substrates for binding to chaperones. Indeed, native proteins are present in a cell at a much higher concentrations relative to misfolded species. Furthermore, if chaperones bind inappropriately to substrates that they are not able to completely unfold, the chaperone molecules may not dissociate rapidly from the partially unfolded species and their activity could get stalled. Another area of question is the role of ATP in the unfolding and refolding of polypeptide substrates. When GroEL/GroES is bound to substrate, ATP hydrolysis leads to conformational changes in GroEL and the release of GroES from the complex. One model is that ATP is not required for the binding of chaperones to misfolded polypeptides but that, at least for some chaperones, ATP hydrolysis is required for the release of the unfolded polypeptide from the chaperone complex so it can refold in solution. Show less
Use the following passage to answer questions:
Under conditions of cell stress, such as exposure to heat, the weak bonds within a protein can be broken, leading to protein misfolding and self-association. When the concentration of misfolded polypeptides becomes high enough, they can form larger aggregates that are very stable because strong bonds occur between the molecules. Many age-related diseases, including Alzheimer's, Parkinson's, and type 2 diabetes, are considered to be the result of protein aggregates, which can eventually cause tissue death. Chaperone molecules bind with high affinity to exposed hydrophobic regions on the surface of misfolded polypeptides and reduce aggregation. However, there is increasing evidence that chaperones do not merely act like sponges that associate with misfolded polypeptides and prevent them from aggregating. Along with a complex of molecules, chaperones can help misfolded substrates unfold and are thus also called unfoldases. Once the substrates are completely unfolded, they can then spontaneously refold into their native conformation. Although chaperones can act on different types of proteins, they unfold them with varying degrees of efficiency. For example, one of the major families of chaperones, which are highly conserved from bacteria to eukaryotes, is called GroEL/GroES. Compared with other chaperones, GroEL/GroES can rapidly convert misfolded rhodanese (rho), a mitochondrial enzyme involved in detoxifying cyanide, into its unfolded form. However, it is unclear in general whether a vast excess of native, properly folded proteins could compete with misfolded substrates for binding to chaperones. Indeed, native proteins are present in a cell at a much higher concentrations relative to misfolded species. Furthermore, if chaperones bind inappropriately to substrates that they are not able to completely unfold, the chaperone molecules may not dissociate rapidly from the partially unfolded species and their activity could get stalled. Another area of question is the role of ATP in the unfolding and refolding of polypeptide substrates. When GroEL/GroES is bound to substrate, ATP hydrolysis leads to conformational changes in GroEL and the release of GroES from the complex. One model is that ATP is not required for the binding of chaperones to misfolded polypeptides but that, at least for some chaperones, ATP hydrolysis is required for the release of the unfolded polypeptide from the chaperone complex so it can refold in solution.
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