Manajit Hayer-Hartl

Bio: Manajit Hayer-Hartl is an academic researcher from Max Planck Society. The author has contributed to research in topics: GroEL & Chaperonin. The author has an hindex of 51, co-authored 98 publications receiving 18130 citations. Previous affiliations of Manajit Hayer-Hartl include Ludwig Maximilian University of Munich & Howard Hughes Medical Institute.

Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein

Abstract: Efficient folding of many newly synthesized proteins depends on assistance from molecular chaperones, which serve to prevent protein misfolding and aggregation in the crowded environment of the cell. Nascent chain–binding chaperones, including trigger factor, Hsp70, and prefoldin, stabilize elongating chains on ribosomes in a nonaggregated state. Folding in the cytosol is achieved either on controlled chain release from these factors or after transfer of newly synthesized proteins to downstream chaperones, such as the chaperonins. These are large, cylindrical complexes that provide a central compartment for a single protein chain to fold unimpaired by aggregation. Understanding how the thousands of different proteins synthesized in a cell use this chaperone machinery has profound implications for biotechnology and medicine.

Molecular chaperones in protein folding and proteostasis

Abstract: Most proteins must fold into defined three-dimensional structures to gain functional activity. But in the cellular environment, newly synthesized proteins are at great risk of aberrant folding and aggregation, potentially forming toxic species. To avoid these dangers, cells invest in a complex network of molecular chaperones, which use ingenious mechanisms to prevent aggregation and promote efficient folding. Because protein molecules are highly dynamic, constant chaperone surveillance is required to ensure protein homeostasis (proteostasis). Recent advances suggest that an age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease. Interventions in these and numerous other pathological states may spring from a detailed understanding of the pathways underlying proteome maintenance.

Molecular Chaperone Functions in Protein Folding and Proteostasis

Abstract: The biological functions of proteins are governed by their three-dimensional fold. Protein folding, maintenance of proteome integrity, and protein homeostasis (proteostasis) critically depend on a complex network of molecular chaperones. Disruption of proteostasis is implicated in aging and the pathogenesis of numerous degenerative diseases. In the cytosol, different classes of molecular chaperones cooperate in evolutionarily conserved folding pathways. Nascent polypeptides interact cotranslationally with a first set of chaperones, including trigger factor and the Hsp70 system, which prevent premature (mis)folding. Folding occurs upon controlled release of newly synthesized proteins from these factors or after transfer to downstream chaperones such as the chaperonins. Chaperonins are large, cylindrical complexes that provide a central compartment for a single protein chain to fold unimpaired by aggregation. This review focuses on recent advances in understanding the mechanisms of chaperone action in promoting and regulating protein folding and on the pathological consequences of protein misfolding and aggregation.

Converging concepts of protein folding in vitro and in vivo

Abstract: Most proteins must fold into precise three-dimensional conformations to fulfill their biological functions. Here we review recent concepts emerging from studies of protein folding in vitro and in vivo, with a focus on how proteins navigate the complex folding energy landscape inside cells with the aid of molecular chaperones. Understanding these reactions is also of considerable medical relevance, as the aggregation of misfolding proteins that escape the cellular quality-control machinery underlies a range of debilitating diseases, including many age-onset neurodegenerative disorders.

In vivo aspects of protein folding and quality control

Abstract: Most proteins must fold into unique three-dimensional structures to perform their biological functions. In the crowded cellular environment, newly synthesized proteins are at risk of misfolding and forming toxic aggregate species. To ensure efficient folding, different classes of molecular chaperones receive the nascent protein chain emerging from the ribosome and guide it along a productive folding pathway. Because proteins are structurally dynamic, constant surveillance of the proteome by an integrated network of chaperones and protein degradation machineries is required to maintain protein homeostasis (proteostasis). The capacity of this proteostasis network declines during aging, facilitating neurodegeneration and other chronic diseases associated with protein aggregation. Understanding the proteostasis network holds the promise of identifying targets for pharmacological intervention in these pathologies.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.

Abstract: The distinct protein aggregates that are found in Alzheimer's, Parkinson's, Huntington's and prion diseases seem to cause these disorders. Small intermediates - soluble oligomers - in the aggregation process can confer synaptic dysfunction, whereas large, insoluble deposits might function as reservoirs of the bioactive oligomers. These emerging concepts are exemplified by Alzheimer's disease, in which amyloid beta-protein oligomers adversely affect synaptic structure and plasticity. Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins.

Protein folding and misfolding

Abstract: The manner in which a newly synthesized chain of amino acids transforms itself into a perfectly folded protein depends both on the intrinsic properties of the amino-acid sequence and on multiple contributing influences from the crowded cellular milieu. Folding and unfolding are crucial ways of regulating biological activity and targeting proteins to different cellular locations. Aggregation of misfolded proteins that escape the cellular quality-control mechanisms is a common feature of a wide range of highly debilitating and increasingly prevalent diseases.

Molecular chaperones in cellular protein folding.

Abstract: The folding of many newly synthesized proteins in the cell depends on a set of conserved proteins known as molecular chaperones. These prevent the formation of misfolded protein structures, both under normal conditions and when cells are exposed to stresses such as high temperature. Significant progress has been made in the understanding of the ATP-dependent mechanisms used by the Hsp70 and chaperonin families of molecular chaperones, which can cooperate to assist in folding new polypeptide chains.