| 1. |
- Babu Moparthi, Satish, et al.
(författare)
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Transient conformational remodeling of folding proteins by GroES - Individually and in concert with GroEL
- 2014
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Ingår i: Journal of chemical biology. - : Springer Berlin/Heidelberg. - 1864-6158 .- 1864-6166. ; 7:1, s. 1-15
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Forskningsöversikt (refereegranskat)abstract
- The commonly accepted dogma of the bacterial GroE chaperonin system entails protein folding mediated by cycles of several ATP-dependent sequential steps where GroEL interacts with the folding client protein. In contrast, we herein report GroES-mediated dynamic remodeling (expansion and compression) of two different protein substrates during folding: the endogenous substrate MreB and carbonic anhydrase (HCAII), a well-characterized protein folding model. GroES was also found to influence GroEL binding induced unfolding and compression of the client protein underlining the synergistic activity of both chaperonins, even in the absence of ATP. This previously unidentified activity by GroES should have important implications for understanding the chaperonin mechanism and cellular stress response. Our findings necessitate a revision of the GroEL/ES mechanism.
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| 2. |
- Hammarström, Per
(författare)
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The Transthyretin Protein and Amyloidosis - an Extraordinary Chemical Biology Platform
- 2024
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Ingår i: Israel Journal of Chemistry. - : WILEY-V C H VERLAG GMBH. - 0021-2148.
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Forskningsöversikt (refereegranskat)abstract
- The amyloidoses are diseases caused by accumulation of amyloid fibrils from over 40 different human misfolded proteins in various organs of the body depending on precursor protein. Amyloidogenesis is a self-perpetuating reaction with deleterious consequences causing degeneration in cells and organs where depositions occur. Transthyretin, TTR, is an amyloidogenic protein causing sporadic disease from the wild-type protein during aging and from numerous different autosomal dominant familial mutations at earlier ages depending on the sequence of the hereditary variant. Until recently the disease process was poorly understood, and therapies were scarce. Over the past decades, spurred by clinical data, using chemical biology research, the mechanisms of TTR production and misfolding have been elucidated affording almost complete coverage of the TTR amyloidogenesis pathway to be targeted. This translational science success has provided a plethora of therapeutic options for the TTR amyloidoses providing an inspiring example for success in previously intractable diseases. image
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| 3. |
- Hammarström, Per, et al.
(författare)
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Viruses and amyloids-a vicious liaison
- 2023
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Ingår i: Prion. - : TAYLOR & FRANCIS INC. - 1933-6896 .- 1933-690X. ; 17:1, s. 82-104
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Forskningsöversikt (refereegranskat)abstract
- The crosstalk between viral infections, amyloid formation and neurodegeneration has been discussed with varying intensity since the last century. Several viral proteins are known to be amyloidogenic. Post-acute sequalae (PAS) of viral infections is known for several viruses. SARS-CoV-2 and COVID-19 implicate connections between amyloid formation and severe outcomes in the acute infection, PAS and neurodegenerative diseases. Is the amyloid connection causation or just correlation? In this review we highlight several aspects where amyloids and viruses meet. The evolutionary driving forces that dictate protein amyloid formation propensity are different for viruses compared to prokaryotes and eukaryotes, while posttranslational endoproteolysis appears to be a common mechanism leading up to amyloid formation for both viral and human proteins. Not only do human and viral proteins form amyloid irrespective of each other but there are also several examples of co-operativity between amyloids, viruses and the inter-, and intra-host spread of the respective entity. Abnormal blood clotting in severe and long COVID and as a side effect in some vaccine recipients has been connected to amyloid formation of both the human fibrin and the viral Spike-protein. We conclude that there are many intersects between viruses and amyloids and, consequently, amyloid and virus research need to join forces here. We emphasize the need to accelerate development and implementation in clinical practice of antiviral drugs to preclude PAS and downstream neurological damage. There is also an ample need for retake on suitable antigen targets for the further development of next generation of vaccines against the current and coming pandemics.
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| 4. |
- Lindgren, Mikael, et al.
(författare)
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Amyloid oligomers: spectroscopic characterization of amyloidogenic protein states
- 2010
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:6, s. 1380-1388
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Forskningsöversikt (refereegranskat)abstract
- It is assumed that protein fibrils manifested in amyloidosis result from an aggregation reaction involving small misfolded protein sequences being in an oligomeric or prefibrillar state. This review covers recent optical spectroscopic studies of amyloid protein misfolding, oligomerization and amyloid fibril growth. Although amyloid fibrils have been studied using established protein-characterization techniques throughout the years, their oligomeric precursor states require sensitive detection in real-time. Here, fluorescent staining is commonly performed using thioflavin T and other small fluorescent molecules such as 4-(dicyanovinyl)- julolidine and 1-amino-8-naphtalene sulphonate that have high affinity to hydrophobic patches. Thus, populated oligomeric intermediates and related prefibrillar structures have been reported for several human amyloidogenic systems, including amyloid-beta protein, prion protein, transthyretin, alpha-synuclein, apolipoprotein C-II and insulin. To obtain information on the progression of the intermediate states, these were monitored in terms of fluorescence parameters, such as anisotropy, and quantum efficiency changes upon protein binding. Recently, new antibody stains have allowed precise monitoring of the oligomer size and distributions using multicolor labelling and single molecule detection. Moreover, a pentameric thiophene derivative (p-FTAA) was reported to indicate early precursors during A-beta(1-40) fibrillation, and was also demonstrated in real-time visualization of cerebral protein aggregates in transgenic AD mouse models by multiphoton microscopy. Conclusively, molecular probes and optical spectroscopy are now entering a phase enabling the in vivo interrogation of the role of oligomers in amyloidosis. Such techniques used in parallel with in vitro experiments, of increasing detail, will probably couple structure to pathogenesis in the near future.
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| 5. |
- Norström, Fredrik, 1974-, et al.
(författare)
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How does unemployment affect self-assessed health? : A systematic review focusing on subgroup effects
- 2014
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 14:1
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Almost all studies on the effect on health from unemployment have concluded that unemployment is bad for your health. However, only a few review articles have dealt with this relation in recent years, and none of them have focused on the analysis of subgroups such as age, gender, and marital status. The objective of our article is to review how unemployment relates to self-assessed health with a focus on its effect on subgroups.METHODS: A search was performed in Web of Science to find articles that measured the effect on health from unemployment. The selection of articles was limited to those written in English, consisting of original data, and published in 2003 or later. Our definition of health was restricted to self-assessed health. Mortality- and morbidity-related measurements were therefore not included in our analysis. For the 41 articles included, information about health measurements, employment status definitions, other factors included in the statistical analysis, study design (including study population), and statistical method were collected with the aim of analysing the results on both the population and factor level.RESULTS: Most of the studies in our review showed a negative effect on health from unemployment on a population basis. Results at the factor levels were most common for gender (25 articles), age (11 articles), geographic location (8 articles), and education level (5 articles). The analysis showed that there was a health effect for gender, age, education level, household income, and geographic location. However, this effect differed between studies and no clear pattern on who benefits or suffers more among these groups could be determined. The result instead seemed to depend on the study context. The only clear patterns of association found were for socioeconomic status (manual workers suffer more), reason for unemployment (being unemployed due to health reasons is worse), and social network (a strong network is beneficial).CONCLUSIONS: Unemployment affects groups of individuals differently. We believe that a greater effort should be spent on specific groups of individuals, such as men or women, instead of the population as a whole when analysing the effect of unemployment on health.
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