| 1. |
- Karki, Sudeep, et al.
(författare)
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Molecular view of ER membrane remodeling by the Sec61/TRAP translocon
- 2023
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Ingår i: EMBO Reports. - 1469-221X. ; 24:12
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Tidskriftsartikel (refereegranskat)abstract
- Protein translocation across the endoplasmic reticulum (ER) membrane is an essential step during protein entry into the secretory pathway. The conserved Sec61 protein-conducting channel facilitates polypeptide translocation and coordinates cotranslational polypeptide-processing events. In cells, the majority of Sec61 is stably associated with a heterotetrameric membrane protein complex, the translocon-associated protein complex (TRAP), yet the mechanism by which TRAP assists in polypeptide translocation remains unknown. Here, we present the structure of the core Sec61/TRAP complex bound to a mammalian ribosome by cryogenic electron microscopy (cryo-EM). Ribosome interactions anchor the Sec61/TRAP complex in a conformation that renders the ER membrane locally thinner by significantly curving its lumenal leaflet. We propose that TRAP stabilizes the ribosome exit tunnel to assist nascent polypeptide insertion through Sec61 and provides a ratcheting mechanism into the ER lumen mediated by direct polypeptide interactions.
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| 2. |
- Kaski, Juan Pablo, et al.
(författare)
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Indications and management of implantable cardioverter-defibrillator therapy in childhood hypertrophic cardiomyopathy
- 2023
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Ingår i: Cardiology in the young. - 1467-1107. ; 33:5, s. 681-698
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Forskningsöversikt (refereegranskat)abstract
- Sudden cardiac death is the most common mode of death during childhood and adolescence in hypertrophic cardiomyopathy, and identifying those individuals at highest risk is a major aspect of clinical care. The mainstay of preventative therapy is the implantable cardioverter-defibrillator, which has been shown to be effective at terminating malignant ventricular arrhythmias in children with hypertrophic cardiomyopathy but can be associated with substantial morbidity. Accurate identification of those children at highest risk who would benefit most from implantable cardioverter-defibrillator implantation while minimising the risk of complications is, therefore, essential. This position statement, on behalf of the Association for European Paediatric and Congenital Cardiology (AEPC), reviews the currently available data on established and proposed risk factors for sudden cardiac death in childhood-onset hypertrophic cardiomyopathy and current approaches for risk stratification in this population. It also provides guidance on identification of individuals at risk of sudden cardiac death and optimal management of implantable cardioverter-defibrillators in children and adolescents with hypertrophic cardiomyopathy.
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