Emma Sierecki
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View article: Divalent and Trivalent Metallic Ions Differentially Affect Alpha-Synuclein Aggregation
Divalent and Trivalent Metallic Ions Differentially Affect Alpha-Synuclein Aggregation Open
Alpha-synuclein (αSyn) is the constituent protein associated with neurodegenerative synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Recent studies have highlighted the potential role o…
View article: Structural Studies of an Anti-necroptosis Viral:Human Functional Hetero-amyloid M45:RIPK3 using SSNMR
Structural Studies of an Anti-necroptosis Viral:Human Functional Hetero-amyloid M45:RIPK3 using SSNMR Open
The formation of RIP-homotypic interaction motif (RHIM)-based heteromeric amyloid assemblies between effector proteins such as RIPK1, ZBP1, or TRIF and the kinase RIPK3 serve as regulating signals for the necroptosis process, a key element…
View article: Signalling by co-operative higher-order assembly formation: linking evidence at molecular and cellular levels
Signalling by co-operative higher-order assembly formation: linking evidence at molecular and cellular levels Open
The concept of higher-order assembly signalling or signalling by co-operative assembly formation (SCAF) was proposed based on the structures of signalling assemblies formed by proteins featuring domains from the death-fold family and the T…
View article: Single-Molecule Fingerprinting Reveals Different Growth Mechanisms in Seed Amplification Assays for Different Polymorphs of α-Synuclein Fibrils
Single-Molecule Fingerprinting Reveals Different Growth Mechanisms in Seed Amplification Assays for Different Polymorphs of α-Synuclein Fibrils Open
α-Synuclein (αSyn) aggregates, detected in the biofluids of patients with Parkinson's disease (PD), have the ability to catalyze their own aggregation, leading to an increase in the number and size of aggregates. This self-templated amplif…
View article: Quantification of nanocondensates formation at the single molecule level
Quantification of nanocondensates formation at the single molecule level Open
Understanding the molecular mechanisms of biomolecular condensate formation through liquid-liquid phase separation is crucial for deciphering cellular cues in normal and pathological contexts. Recent studies have highlighted the existence …
View article: Single molecule fingerprinting reveals different growth mechanisms in seed amplification assays for different polymorphs of αSynuclein fibrils
Single molecule fingerprinting reveals different growth mechanisms in seed amplification assays for different polymorphs of αSynuclein fibrils Open
Alpha-synuclein (αSyn) aggregates, detected in the biofluids of patients with Parkinson’s disease, have the ability to catalyze their own aggregation, leading to an increase in the number and size of aggregates. This self-templated amplifi…
View article: The HIV capsid mimics karyopherin engagement of FG-nucleoporins
The HIV capsid mimics karyopherin engagement of FG-nucleoporins Open
HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus 1,2 . Remarkably, the intact HIV capsid is more than 1,000 times lar…
View article: α-Synuclein Strains and Their Relevance to Parkinson’s Disease, Multiple System Atrophy, and Dementia with Lewy Bodies
α-Synuclein Strains and Their Relevance to Parkinson’s Disease, Multiple System Atrophy, and Dementia with Lewy Bodies Open
Like many neurodegenerative diseases, Parkinson’s disease (PD) is characterized by the formation of proteinaceous aggregates in brain cells. In PD, those proteinaceous aggregates are formed by the α-synuclein (αSyn) and are considered the …
View article: Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates
Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates Open
The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organisation and dynamics of chromatin c…
View article: Karyopherin mimicry explains how the HIV capsid penetrates nuclear pores
Karyopherin mimicry explains how the HIV capsid penetrates nuclear pores Open
Summary Paragraph HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus. Remarkably, the intact HIV capsid is over one tho…
View article: The blood vasculature instructs lymphatic patterning in a SOX7‐dependent manner
The blood vasculature instructs lymphatic patterning in a SOX7‐dependent manner Open
Despite a growing catalog of secreted factors critical for lymphatic network assembly, little is known about the mechanisms that modulate the expression level of these molecular cues in blood vascular endothelial cells (BECs). Here, we sho…
View article: Evolutionary Landscape of SOX Genes to Inform Genotype-to-Phenotype Relationships
Evolutionary Landscape of SOX Genes to Inform Genotype-to-Phenotype Relationships Open
The SOX transcription factor family is pivotal in controlling aspects of development. To identify genotype–phenotype relationships of SOX proteins, we performed a non-biased study of SOX using 1890 open-reading frame and 6667 amino acid se…
View article: The RHIM of the Immune Adaptor Protein TRIF Forms Hybrid Amyloids with Other Necroptosis-Associated Proteins
The RHIM of the Immune Adaptor Protein TRIF Forms Hybrid Amyloids with Other Necroptosis-Associated Proteins Open
TIR-domain-containing adapter-inducing interferon-β (TRIF) is an innate immune protein that serves as an adaptor for multiple cellular signalling outcomes in the context of infection. TRIF is activated via ligation of Toll-like receptors 3…
View article: Single Molecule Fingerprinting Reveals Different Amplification Properties of α-Synuclein Oligomers and Preformed Fibrils in Seeding Assay
Single Molecule Fingerprinting Reveals Different Amplification Properties of α-Synuclein Oligomers and Preformed Fibrils in Seeding Assay Open
The quantification of α-synuclein aggregates has emerged as a promising biomarker for synucleinopathies. Assays that amplify and detect such aggregates have revealed the presence of seeding-competent species in biosamples of patients diagn…
View article: Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential
Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential Open
SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved und…
View article: A dominant-negative SOX18 mutant disrupts multiple regulatory layers essential to transcription factor activity
A dominant-negative SOX18 mutant disrupts multiple regulatory layers essential to transcription factor activity Open
Few genetically dominant mutations involved in human disease have been fully explained at the molecular level. In cases where the mutant gene encodes a transcription factor, the dominant-negative mode of action of the mutant protein is par…
View article: MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography
MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography Open
Myeloid differentiation primary response gene 88 (MyD88) and MyD88 adaptor-like/TIRAP (MAL) are Toll-like receptor (TLR) adaptors that signal to induce proinflammatory cytokine production.The TLR responds to a pathogen or endogenous molecu…
View article: MyD88 TIR domain higher-order assembly interactions revealed by serial femtosecond crystallography
MyD88 TIR domain higher-order assembly interactions revealed by serial femtosecond crystallography Open
MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production.We previously observed that the TIR domain of MAL (MAL TIR ) forms filaments in vitro and induces formation of crystalline highe…
View article: Single molecule fingerprinting reveals different amplification properties of α-synuclein oligomers and preformed fibrils in seeding assay
Single molecule fingerprinting reveals different amplification properties of α-synuclein oligomers and preformed fibrils in seeding assay Open
The quantification of α-synuclein (α-syn) aggregates has emerged as a promising biomarker for synucleinopathies. Assays that amplify and detect such aggregates have revealed the presence of seeding-competent species in biosamples of patien…
View article: The blood vasculature instructs lymphatics patterning in a SOX7 dependent manner
The blood vasculature instructs lymphatics patterning in a SOX7 dependent manner Open
Despite a growing catalogue of secreted factors critical for lymphatic network assembly, little is known about the mechanisms that modulate the expression level of these molecular cues in blood vascular endothelial cells (BECs). Here, we s…
View article: Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response
Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response Open
Caveolae-associated protein 3 (cavin3) is inactivated in most cancers. We characterized how cavin3 affects the cellular proteome using genome-edited cells together with label-free quantitative proteomics. These studies revealed a prominent…
View article: Author response: Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response
Author response: Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response Open
Article Figures and data Abstract eLife digest Introduction Results Discussion Materials and methods Appendix 1 Data availability References Decision letter Author response Article and author information Metrics Abstract Caveolae-associate…
View article: MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography.
MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography. Open
MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MALTIR) forms filaments in vitro and induces formation of crystalline higher…
View article: Rapid HIV-1 Capsid Interaction Screening Using Fluorescence Fluctuation Spectroscopy
Rapid HIV-1 Capsid Interaction Screening Using Fluorescence Fluctuation Spectroscopy Open
The HIV capsid is a multifunctional protein capsule that mediates the delivery of the viral genetic material into the nucleus of the target cell. Host cell proteins bind to a number of repeating binding sites on the capsid to regulate step…
View article: Single‐Molecule Counting Coupled to Rapid Amplification Enables Detection of α‐Synuclein Aggregates in Cerebrospinal Fluid of Parkinson's Disease Patients
Single‐Molecule Counting Coupled to Rapid Amplification Enables Detection of α‐Synuclein Aggregates in Cerebrospinal Fluid of Parkinson's Disease Patients Open
α‐Synuclein aggregation is a hallmark of Parkinson's disease and a promising biomarker for early detection and assessment of disease progression. The prospect of a molecular test for Parkinson's disease is materializing with the recent dev…
View article: Selectivity of Protein Interactions along the Aggregation Pathway of α-Synuclein
Selectivity of Protein Interactions along the Aggregation Pathway of α-Synuclein Open
The aggregation of α-SYN follows a cascade of oligomeric, prefibrillar and fibrillar forms, culminating in the formation of Lewy Bodies (LB), the pathological hallmarks of Parkinson’s Disease in neurons. Whilst α-synuclein is a major contr…