A5037582413- Heat shock proteins research
- Protein Structure and Dynamics
- Lipoproteins and Cardiovascular Health
- Toxin Mechanisms and Immunotoxins
- Viral Infectious Diseases and Gene Expression in Insects
- Computational Drug Discovery Methods
- Prion Diseases and Protein Misfolding
- Antioxidant Activity and Oxidative Stress
- Cancer, Lipids, and Metabolism
- Enzyme Structure and Function
- Trace Elements in Health
- RNA and protein synthesis mechanisms
- Bacillus and Francisella bacterial research
- Plant biochemistry and biosynthesis
- Porphyrin Metabolism and Disorders
- RNA Research and Splicing
- Kidney Stones and Urolithiasis Treatments
- Genetic factors in colorectal cancer
- Proteins in Food Systems
- Alzheimer's disease research and treatments
- Metabolomics and Mass Spectrometry Studies
- Insect Resistance and Genetics
- Protein purification and stability
- ATP Synthase and ATPases Research
- Mass Spectrometry Techniques and Applications
Instituto Biofisika
2016-2024
University of the Basque Country
2010-2024
Fundación Biofísica Bizkaia
2011-2021
Abstract J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, structure and function many remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures can be dissociated by Hsc70, constitutively expressed Hsp70 isoform. Cryoelectron microscopy mutational studies reveal different domains are involved self-association. Oligomer dissociation into dimers potentiates its...
Significance Although the human disaggregase machinery has been shown to disassemble mature α-synuclein amyloid fibrils, molecular mechanism that drives process remained elusive. In this work, we show disassembly is initiated by destabilization of fibril ends, followed fast propagation protofilament unzipping and depolymerization along axis. This results in an all-or-none disaggregation individual aggregates, avoiding accumulation harmful intermediate aggregated species. We specifically...
Abstract Familial hypercholesterolaemia (FH) is an inherited autosomal dominant disorder resulting from defects in the low-density lipoprotein receptor ( LDLR ), apolipoprotein B APOB ) or proprotein convertase subtilisin/kexin type 9 PCSK9 genes. In majority of cases FH caused by mutations occurring within , while only few and have been proved to cause disease. p.(Arg3527Gln) was first mutation being identified characterized. Recently two novel pathogenic variants described: p.(Arg1164Thr)...
Untreated familial hypercholesterolemia (FH) leads to atherosclerosis and early cardiovascular disease. Mutations in the low-density lipoprotein receptor (LDLr) gene constitute major cause of FH, high number mutations already described LDLr makes necessary cascade screening or vitro functional characterization provide a definitive diagnosis. Implementation high-predicting capacity software constitutes valuable approach for assessing pathogenicity variants help diagnosis management FH This...
The hexameric AAA+ (ATPase associated with various cellular activities) chaperone ClpB reactivates protein aggregates in collaboration the DnaK system. An intriguing aspect of function is that active hexamer unstable and therefore questions how this uses multiple rounds ATP hydrolysis to translocate substrates through its central channel. In present paper, we report use biochemical fluorescence tools explore dynamics under different experimental conditions. analysis activity kinetics subunit...
ClpB is a member of the AAA+ superfamily that forms ring‐shaped homohexamer. Each protomer contains two nucleotide binding domains arranged in rings hydrolyze ATP. We extend here previous studies on utilization requirements by using an experimental approach maximizes random incorporation different subunits into protein hexamer. Incorporation one subunit unable to bind or ATP knocks down chaperone activity, while wt hexamer can accommodate mutant only ring. Four seem build functional...
Abstract Acidification in the endosome causes lipoprotein release by promoting a conformational change LDLR allowing its recycling and degradation of LDL. Notwithstanding changes occurring have expanded considerably, structural LDL particles not been fully explored yet. The objectives present work were to study apoB100 infrared spectroscopy (IR) also size morphology dynamic light scattering (DLS) electron microscopy (EM) at both pH 7.4 5.0. We determined IR that acidification from 5.0,...
The chaperone ClpB in bacteria is responsible for the reactivation of aggregated proteins collaboration with DnaK system. Association these chaperones at aggregate surface stimulates ATP hydrolysis, which mediates substrate remodeling. However, a question that remains unanswered whether bichaperone complex can be selectively activated by substrates require We find large aggregates or bulky, native-like activates complex, whereas smaller, permanently unfolded protein extended, short peptides...
The aggregation of α-synuclein is the hallmark a collective neurodegenerative disorders known as synucleinopathies. tendency to aggregate this protein, toxicity its intermediates and ability cellular protein quality control system clear these seems be regulated, among other factors, by post-translational modifications (PTMs). Among modifications, we consider herein proteolysis at both N- C-terminal regions factor that could modulate disassembly toxic amyloids human disaggregase, combination...
Lipoproteins are responsible for cholesterol traffic in humans. Low density lipoprotein (LDL) delivers from liver to peripheral tissues. A misleading delivery can lead the formation of atherosclerotic plaques. LDL has a single protein, apoB-100, that binds specific receptor. It is known failure associated with deficient protein-receptor binding leads plaque formation. ApoB-100 large lipid-associated polypeptide difficulting study its structure. IR spectroscopy technique suitable follow...
ABSTRACTInfrared structural analysis usually implies a mathematical approach to extract the information contained in protein amide bands. Thermal profiles have been used help understanding of stability. A new approach, generalized 2D- IR correlational spectroscopy, has recently introduced. This performs correlation dynamic fluctuations caused by an external perturbation, enhance spectral resolution. By using combination these three approaches we studied thermal unfolding several soluble and...