Conformational and dynamic properties of the KH1 domain of FMRP and its fragile X syndrome linked G266E variant
This study aims to elucidate the molecular mechanism underlying the loss of function associated with the G266EKH1 pathological variant. We investigate the conformational and dynamical properties of the isolated KH1 domain and the two KH1 site-directed mutants G266EKH1 and G266AKH1. Employing a combined in vitro and in silico approach, we reveal that the G266EKH1 variant lacks the characteristic features of a folded domain. This observation provides an explanation for functional impairment observed in FMRP carrying the G266E mutation within the KH1 domain, as it renders the domain unable to fold properly. Molecular Dynamics...
Source: Biochimica et Biophysica Acta - April 19, 2024 Category: Biochemistry Authors: Flavia Catalano Daniele Santorelli Alessandra Astegno Filippo Favaretto Marco D'Abramo Alessandra Del Giudice Maria Laura De Sciscio Francesca Troilo Giorgio Giardina Adele Di Matteo Carlo Travaglini-Allocatelli Source Type: research
Chemical proteomics approaches for protein post-translational modification studies
Biochim Biophys Acta Proteins Proteom. 2024 Apr 18;1872(4):141017. doi: 10.1016/j.bbapap.2024.141017. Online ahead of print.ABSTRACTThe diversity and dynamics of proteins play essential roles in maintaining the basic constructions and functions of cells. The abundance of functional proteins is regulated by the transcription and translation processes, while the alternative splicing enables the same gene to generate distinct protein isoforms of different lengths. Beyond the transcriptional and translational regulations, post-translational modifications (PTMs) are able to further expand the diversity and functional scope of p...
Source: Biochimica et Biophysica Acta - April 19, 2024 Category: Biochemistry Authors: Nan Zhang Jinghua Wu Qingfei Zheng Source Type: research
The molecular interplay between human and bacterial amyloids: Implications in neurodegenerative diseases
Biochim Biophys Acta Proteins Proteom. 2024 Apr 17;1872(4):141018. doi: 10.1016/j.bbapap.2024.141018. Online ahead of print.ABSTRACTNeurodegenerative disorders such as Parkinson's (PD) and Alzheimer's diseases (AD) are linked with the assembly and accumulation of proteins into structured scaffold called amyloids. These diseases pose significant challenges due to their complex and multifaceted nature. While the primary focus has been on endogenous amyloids, recent evidence suggests that bacterial amyloids may contribute to the development and exacerbation of such disorders. The gut-brain axis is emerging as a communication ...
Source: Biochimica et Biophysica Acta - April 19, 2024 Category: Biochemistry Authors: Neha Jain Source Type: research
The human testis-enriched HSPA2 interacts with HIF-1 α in epidermal keratinocytes, yet HIF-1α stability and HIF-1-dependent gene expression rely on the HSPA (HSP70) activity
In this study, we revealed that HIF-1α is the first confirmed client of HSPA2 in human somatic cells. It colocalises and interacts directly with HSPA2 in the epidermis in situ and immortalised keratinocytes in vitro. Using an in vitro model based on HSPA2-overexpressing and HSPA2-deficient variants of immortalised keratinocytes we showed that changes in HSPA2 levels do not affect the levels and intracellular localisation of HIF-1α or influence the ability of HIF-1 to modulate target gene expression. However, HIF-1α stability in keratinocytes appears critically reliant on HSPAs as a group of functionally overlapping chap...
Source: Biochimica et Biophysica Acta - April 19, 2024 Category: Biochemistry Authors: Damian Robert Sojka Agnieszka Gogler Daria Kania Natalia Vydra Klaudia Wiecha Ma łgorzata Adamiec-Organiściok Agata Wilk Vira Chumak Damian Maty śniak Dorota Scieglinska Source Type: research
Mitochondria function in cytoplasmic FeS protein biogenesis
Biochim Biophys Acta Mol Cell Res. 2024 Apr 17:119733. doi: 10.1016/j.bbamcr.2024.119733. Online ahead of print.ABSTRACTIron‑sulfur (FeS) clusters are cofactors of numerous proteins involved in various essential functions including cellular respiration, protein translation, DNA synthesis and repair, ribosome maturation, anti-viral responses, and isopropylmalate isomerase activity. Novel FeS cluster proteins are still being discovered due to the widespread use of cryogenic electron microscopy (cryo-EM) and elegant genetic screens targeted at protein discovery. A complex sequence of biochemical reactions mediated by a cons...
Source: Biochimica et Biophysica Acta - April 19, 2024 Category: Biochemistry Authors: Andrew Dancis Ashutosh K Pandey Debkumar Pain Source Type: research
The role of nucleotide opening dynamics in facilitated target search by DNA-repair proteins
In this study, we employ extensive molecular dynamics simulations using an appropriately tuned model of both protein and DNA to probe the underlying molecular principles. Our findings reveal that the dynamics of a non-canonical base generate an entropic signal that guides the one-dimensional search of a repair protein, thereby facilitating the recognition of the lesion site. The width of the funnel perfectly aligns with the one-dimensional diffusion length of DNA-binding proteins. The generic mechanism provides a physical basis for rapid recognition and specificity of DNA damage sensing and recognition.PMID:38641240 | DOI:...
Source: Biochimica et Biophysica Acta - April 19, 2024 Category: Biochemistry Authors: Sujeet Kumar Mishra None Sangeeta Dieter W Heermann Arnab Bhattacherjee Source Type: research
Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 16;1870(5):167178. doi: 10.1016/j.bbadis.2024.167178. Online ahead of print.ABSTRACTPitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by haploinsufficiency of transcription factor 4 (TCF4). In this work, we focused on the cerebral cortex and investigated in detail the progenitor cell dynamics and the outcome of neurogenesis in a PTHS mouse model. Labeling and quantification of progenitors and newly generated neurons at various time points during embryonic development revealed alterations affecting the dynamic of cortical progenitors since the earliest stages o...
Source: Biochimica et Biophysica Acta - April 18, 2024 Category: Biochemistry Authors: Francisca Espinoza Ram ón Carrazana Eduardo Retamal-Fredes Denisse Ávila Fabio Papes Alysson R Muotri Ariel Ávila Source Type: research
Molecular and cellular consequences of mevalonate kinase deficiency
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 16;1870(5):167177. doi: 10.1016/j.bbadis.2024.167177. Online ahead of print.ABSTRACTMevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder associated with recurrent autoinflammatory episodes. The disorder is caused by bi-allelic loss-of-function variants in the MVK gene, which encodes mevalonate kinase (MK), an early enzyme in the isoprenoid biosynthesis pathway. To identify molecular and cellular consequences of MKD, we studied primary fibroblasts from severely affected patients with mevalonic aciduria (MKD-MA) and more mildly affected patients with hyp...
Source: Biochimica et Biophysica Acta - April 18, 2024 Category: Biochemistry Authors: Frouwkje A Politiek Marjolein Turkenburg Linda Henneman Rob Ofman Hans R Waterham Source Type: research
Epigenetic arsenal for stress mitigation in plants
Biochim Biophys Acta Gen Subj. 2024 Apr 16;1868(7):130620. doi: 10.1016/j.bbagen.2024.130620. Online ahead of print.ABSTRACTPlant's ability to perceive, respond to, and ultimately adapt to various stressors is a testament to their remarkable resilience. In response to stresses, plants activate a complex array of molecular and physiological mechanisms. These include the rapid activation of stress-responsive genes, the manufacturing of protective compounds, modulation of cellular processes and alterations in their growth and development patterns to enhance their chances of survival. Epigenetic mechanisms play a pivotal role ...
Source: Biochimica et Biophysica Acta - April 18, 2024 Category: Biochemistry Authors: Aishwarya Ashok Gaude Roxiette Heromina Siqueira Savia Bernadette Botelho Siddhi Kashinath Jalmi Source Type: research
The essential link: How STAT3 connects tumor metabolism to immunity
Biochim Biophys Acta Gene Regul Mech. 2024 Apr 16;1867(2):195028. doi: 10.1016/j.bbagrm.2024.195028. Online ahead of print.ABSTRACTImmunotherapy is a promising and long-lasting tumor treatment method, but it is challenged by the complex metabolism of tumors. To optimize immunotherapy, it is essential to further investigate the key proteins that regulate tumor metabolism and immune response. STAT3 plays a crucial role in regulating tumor dynamic metabolism and affecting immune cell function by responding to various cytokines and growth factors, which can be used as a potential target for immunotherapy. This review focuses o...
Source: Biochimica et Biophysica Acta - April 18, 2024 Category: Biochemistry Authors: Shu Zhong Jingjing Tong Source Type: research
Human oligodendrocyte-like cell differentiation is promoted by TSPO-mediated endogenous steroidogenesis
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 15:167174. doi: 10.1016/j.bbadis.2024.167174. Online ahead of print.ABSTRACTMature oligodendrocytes (OLs) arise from oligodendrocyte precursor cells that, in case of demyelination, are recruited at the lesion site to remyelinate the axons and therefore restore the transmission of nerve impulses. It has been widely documented that exogenously administered steroid molecules are potent inducers of myelination. However, little is known about how neurosteroids produced de novo by OLs can impact this process. Here, we employed a human OL precursor cell line to investigate the role of ...
Source: Biochimica et Biophysica Acta - April 17, 2024 Category: Biochemistry Authors: Chiara Tremolanti Elisa Angeloni Eleonora Da Pozzo Lorenzo Germelli Chiara Giacomelli Eduardo Scalzi Sabrina Taliani Federico Da Settimo Ayiko é-Guy Mensah-Nyagan Claudia Martini Barbara Costa Source Type: research
Urotensin II receptor deficiency ameliorates ligation-induced carotid intimal hyperplasia partially through the RhoA-YAP1 pathway
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 15;1870(5):167170. doi: 10.1016/j.bbadis.2024.167170. Online ahead of print.ABSTRACTIntimal hyperplasia (IH) is a common pathological feature of vascular proliferative diseases, such as atherosclerosis and restenosis after angioplasty. Urotensin II (UII) and its receptor (UTR) are widely expressed in cardiovascular tissues. However, it remains unclear whether the UII/UTR system is involved in IH. Right unilateral common carotid artery ligation was performed and maintained for 21 days to induce IH in UTR knockout (UTR-/-) and wild-type (WT) mice. Histological analysis revealed th...
Source: Biochimica et Biophysica Acta - April 17, 2024 Category: Biochemistry Authors: Panpan Wei Kangli Tian Haole Liu Kexin Li Naqash Alam Daxin Cheng Meng Li Xue He Jia Guo Rong Wang Weirong Wang Liang Bai Enqi Liu Baohui Xu Yankui Li Sihai Zhao Source Type: research
Mitochondrial calcium signaling in non-neuronal cells: Implications for Alzheimer's disease pathogenesis
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 15;1870(5):167169. doi: 10.1016/j.bbadis.2024.167169. Online ahead of print.ABSTRACTMitochondrial dysregulation is pivotal in Alzheimer's disease (AD) pathogenesis. Calcium governs vital mitochondrial processes impacting energy conversion, oxidative stress, and cell death signaling. Disruptions in mitochondrial calcium (mCa2+) handling induce calcium overload and trigger the opening of mitochondrial permeability transition pore, ensuing energy deprivation and resulting in AD-related neuronal cell death. However, the role of mCa2+ in non-neuronal cells (microglia, astrocytes, oli...
Source: Biochimica et Biophysica Acta - April 17, 2024 Category: Biochemistry Authors: Darpan Raghav Shatakshi Shukla Pooja Jadiya Source Type: research
The paradox of fatty-acid β-oxidation in muscle insulin resistance: Metabolic control and muscle heterogeneity
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 15:167172. doi: 10.1016/j.bbadis.2024.167172. Online ahead of print.ABSTRACTThe skeletal muscle is a metabolically heterogeneous tissue that plays a key role in maintaining whole-body glucose homeostasis. It is well known that muscle insulin resistance (IR) precedes the development of type 2 diabetes. There is a consensus that the accumulation of specific lipid species in the tissue can drive IR. However, the role of the mitochondrial fatty-acid β-oxidation in IR and, consequently, in the control of glucose uptake remains paradoxical: interventions that either inhibit or activa...
Source: Biochimica et Biophysica Acta - April 17, 2024 Category: Biochemistry Authors: Marcel A Vieira-Lara Barbara M Bakker Source Type: research
Caveolin-2 palmitoylation turnover facilitates insulin receptor substrate-1-directed lipid metabolism by insulin receptor tyrosine kinase
Biochim Biophys Acta Mol Basis Dis. 2024 Apr 15:167173. doi: 10.1016/j.bbadis.2024.167173. Online ahead of print.ABSTRACTHere, we show that insulin induces palmitoylation turnover of Caveolin-2 (Cav-2) in adipocytes. Acyl protein thioesterases-1 (APT1) catalyzes Cav-2 depalmitoylation, and zinc finger DHHC domain-containing protein palmitoyltransferase 21 (ZDHHC21) repalmitoylation of the depalmitoylated Cav-2 for the turnover, thereby controlling insulin receptor (IR)-Cav-2-insulin receptor substrate-1 (IRS-1)-Akt-driven signaling. Insulin-induced palmitoylation turnover of Cav-2 facilitated glucose uptake and fat storage...
Source: Biochimica et Biophysica Acta - April 17, 2024 Category: Biochemistry Authors: Moonjeong Choi Jaewoong Lee Kyuho Jeong Yunbae Pak Source Type: research
