Molecular chaperones are multidomain proteins that assist in protein folding, prevent aggregation, and mediate unfolding and disassembly. They are essential for maintaining protein homeostasis (proteostasis) and cellular health. Unlike enzymes, chaperones are large, dynamic molecular machines that operate on a wide range of substrates. Their mechanisms involve structural changes and domain movements, often facilitated by ATP binding and hydrolysis. Chaperones are crucial for protein quality control, ensuring correct folding and function, and mitigating the harmful effects of protein misfolding and aggregation, which can lead to neurodegenerative diseases. Key chaperone families include HSP60, HSP70, HSP90, and HSP100. HSP70 is the most abundant chaperone and plays a central role in protein folding, translocation, and disaggregation. It interacts with various cofactors, including HSP40 and NEFs, to regulate its activity. HSP70 has two domains: an ATPase domain and a substrate-binding domain, which interact dynamically to facilitate folding. HSP90 is a flexible, dynamic chaperone involved in signaling and the maturation of key proteins, including steroid hormone receptors and oncogenic proteins. It functions in a complex network of interactions with co-chaperones and client proteins. HSP60 forms a symmetrical complex that provides a protected environment for protein folding. It acts in a coordinated manner to assist in the folding of proteins. HSP100 is a sequential unfolding machine that works with other chaperones to disassemble aggregates and prevent toxic effects. The mechanisms of these chaperones involve ATP-dependent processes, domain movements, and allosteric regulation. The structural basis of their function is being elucidated through studies of their domains and interactions with substrates. Chaperones are highly dynamic and their structures are often in a state of rapid fluctuation. The ATPase domains of chaperones are not tightly coupled to their nucleotide states, allowing for flexible and dynamic interactions. The HSP70 family, in particular, has been studied extensively, revealing the importance of domain interactions and allosteric regulation in its function. The HSP90 family is also highly dynamic, with a complex network of interactions that regulate its activities. The HSP60 and HSP100 families are more specialized, with HSP60 providing a protected environment for folding and HSP100 facilitating the disassembly of aggregates. The roles and mechanisms of these chaperone families are critical for maintaining cellular function and preventing protein misfolding diseases. Understanding their structures and interactions is essential for developing therapeutic strategies to combat protein misfolding disorders. Current research focuses on high-resolution structures of chaperone complexes, the identification of specific pathways in aggregate toxicity, and the regulation of proteostasis. These studies provide insights into the dynamic nature of chaperMolecular chaperones are multidomain proteins that assist in protein folding, prevent aggregation, and mediate unfolding and disassembly. They are essential for maintaining protein homeostasis (proteostasis) and cellular health. Unlike enzymes, chaperones are large, dynamic molecular machines that operate on a wide range of substrates. Their mechanisms involve structural changes and domain movements, often facilitated by ATP binding and hydrolysis. Chaperones are crucial for protein quality control, ensuring correct folding and function, and mitigating the harmful effects of protein misfolding and aggregation, which can lead to neurodegenerative diseases. Key chaperone families include HSP60, HSP70, HSP90, and HSP100. HSP70 is the most abundant chaperone and plays a central role in protein folding, translocation, and disaggregation. It interacts with various cofactors, including HSP40 and NEFs, to regulate its activity. HSP70 has two domains: an ATPase domain and a substrate-binding domain, which interact dynamically to facilitate folding. HSP90 is a flexible, dynamic chaperone involved in signaling and the maturation of key proteins, including steroid hormone receptors and oncogenic proteins. It functions in a complex network of interactions with co-chaperones and client proteins. HSP60 forms a symmetrical complex that provides a protected environment for protein folding. It acts in a coordinated manner to assist in the folding of proteins. HSP100 is a sequential unfolding machine that works with other chaperones to disassemble aggregates and prevent toxic effects. The mechanisms of these chaperones involve ATP-dependent processes, domain movements, and allosteric regulation. The structural basis of their function is being elucidated through studies of their domains and interactions with substrates. Chaperones are highly dynamic and their structures are often in a state of rapid fluctuation. The ATPase domains of chaperones are not tightly coupled to their nucleotide states, allowing for flexible and dynamic interactions. The HSP70 family, in particular, has been studied extensively, revealing the importance of domain interactions and allosteric regulation in its function. The HSP90 family is also highly dynamic, with a complex network of interactions that regulate its activities. The HSP60 and HSP100 families are more specialized, with HSP60 providing a protected environment for folding and HSP100 facilitating the disassembly of aggregates. The roles and mechanisms of these chaperone families are critical for maintaining cellular function and preventing protein misfolding diseases. Understanding their structures and interactions is essential for developing therapeutic strategies to combat protein misfolding disorders. Current research focuses on high-resolution structures of chaperone complexes, the identification of specific pathways in aggregate toxicity, and the regulation of proteostasis. These studies provide insights into the dynamic nature of chaper