A5083952456- Ubiquitin and proteasome pathways
- Cerebrovascular and genetic disorders
- Protease and Inhibitor Mechanisms
- S100 Proteins and Annexins
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Advanced Proteomics Techniques and Applications
- Enzyme Structure and Function
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- RNA Research and Splicing
- Phagocytosis and Immune Regulation
- Bioinformatics and Genomic Networks
- SARS-CoV-2 and COVID-19 Research
- Chemical Synthesis and Analysis
- RNA modifications and cancer
- Influenza Virus Research Studies
- Microbial Metabolic Engineering and Bioproduction
- Neurobiology and Insect Physiology Research
- Fungal and yeast genetics research
- Machine Learning in Bioinformatics
- Protein Kinase Regulation and GTPase Signaling
- COVID-19 Clinical Research Studies
- Erythrocyte Function and Pathophysiology
Uppsala University
2020-2024
University of Copenhagen
2024
The spike protein of SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on host cell surface and subsequently enters cells through receptor-mediated endocytosis. Additional receptors may be directly or indirectly involved, including integrins. cytoplasmic tails ACE2 integrins contain several predicted short linear motifs (SLiMs) that facilitate internalization virus as well its subsequent propagation processes such autophagy. Here, we measured binding affinity interactions between...
Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class protein-protein interactions. Uncovering mediated interactions provides both a molecular understanding viral with their and the foundation for developing novel antiviral reagents. Here we describe discovery approach covering 23 coronavirus strains that high resolution information on direct virus-host We 269...
Abstract Phosphorylation is a ubiquitous post‐translation modification that regulates protein function by promoting, inhibiting or modulating protein–protein interactions. Hundreds of thousands phosphosites have been identified but the vast majority not functionally characterised and it remains challenge to decipher phosphorylation events We generated phosphomimetic proteomic peptide‐phage display library screen for modulate short linear motif‐based The peptidome covers ~13,500...
Significance Protein function can be allosterically regulated by changes in structure or dynamics. PDZ domains are classic examples for studies of allostery single protein domains. However, often found multidomain proteins; particular, PDZ3 is located a supramodule containing three The allosteric network has never been studied the presence adjacent Here we map PDZ3:ligand complex, both isolation and context supramodule. We demonstrate that highly dependent on this supertertiary structure,...
Low affinity and transient protein-protein interactions, such as short linear motif (SLiM)-based require dedicated experimental tools for discovery validation. Here, we evaluated compared biotinylated peptide pulldown protein interaction screen on matrix (PRISMA) coupled to mass-spectrometry (MS) using a set of peptides containing motifs. Eight different sequences that engage in interactions with three distinct domains (KEAP1 Kelch, MDM2 SWIB, TSG101 UEV) wide range affinities were tested....
Short linear motifs (SLiMs) are the most ubiquitous protein interaction modules in unstructured regions of human proteome. Despite their central role function, our understanding contribution SLiMs to cellular homeostasis remains limited. To address this, we designed base editor libraries precisely mutate all curated and a set computationally predicted instances defined by SLiM-like evolutionary patterns. By targeting 7,293 SLiM containing with 80,473 mutations, define dependency map...
Abstract Specific protein-protein interactions are central to all processes that underlie cell physiology. Numerous studies using a wide range of experimental approaches have identified tens thousands human interactions. However, many remain be discovered, and low affinity, conditional type-specific likely disproportionately under-represented. Moreover, for most known the binding regions uncharacterized. We previously developed proteomic peptide phage display (ProP-PD), method simultaneous...
Abstract Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, current methods do not identify this important class protein-protein interactions. Uncovering mediated interactions provides both a molecular understanding viral with their and the foundation for developing novel antiviral reagents. Here we describe scalable discovery approach covering 229 RNA viruses that high resolution information on direct virus-host We 269...
Cyclin-CDKs are master regulators of cell division. In addition to directly activating the CDK, cyclin subunit regulates CDK specificity by binding short peptide "docking" motifs in substrates. Here, we measure relative strength ∼100,000 peptides 11 human cyclins from five families (D, E, A, B and F). Using a quantitative intracellular assay large-scale tiled screening, identified range non-canonical binders that unveil broader than anticipated repertoire docking motif types. Structural...
Abstract Whole genome and exome sequencing are reporting on hundreds of thousands missense mutations. Taking a pan-disease approach, we explored how mutations in the intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created peptide-phage display library tiling ∼57,000 peptides from IDRs human proteome overlapping 12,301 single nucleotide variant associated with diverse phenotypes including cancer, metabolic diseases...
Abstract Phosphorylation is an extensively studied post-translation modification that regulates protein function by promoting, inhibiting or modulating protein-protein interactions. Deciphering which of the hundreds thousands phosphosites in proteome regulate interactions remains challenging. We generated a proteomic peptide-phage display (ProP-PD) library to screen for short linear motif-based The phage peptidome covers 13,500 phospho-serine/threonine sites found intrinsically disordered...
Abstract The notion that protein function is allosterically regulated by structural or dynamic changes in proteins has been extensively investigated several domains isolation. In particular, PDZ have represented a paradigm for these studies, despite providing conflicting results. Furthermore, it still unknown how the association between supramodules, consitituting so-called supertertiary structure, affects allosteric networks. Here, we experimentally mapped network PDZ:ligand complex, both...
Abstract The spike protein of the SARS-CoV-2 interacts with angiotensin converting enzyme 2 (ACE2) and enters host cell by receptor-mediated endocytosis. Concomitantly, evidence is pointing to involvement additional receptors, such as integrins. cytoplasmic tails ACE2 integrin β3 contain a plethora predicted binding motifs. Here, we confirm functionality some these motifs through affinity measurements. class I PDZ motif in tail binds first domain scaffold NHERF3. clathrin-adaptor subunit AP2...
Abstract Low affinity and transient protein-protein interactions, such as short linear motif (SLiM)-based require dedicated experimental tools for discovery validation. Here, we evaluated compared biotinylated peptide pulldown protein interaction screen on matrix (PRISMA) coupled to mass-spectrometry (MS) using a set of peptides containing motifs. Eight different sequences that engage in interactions with three distinct domains (KEAP1 Kelch, MDM2 SWIB, TSG101 UEV) wide range affinities were...