A. J. R. Heck

Dual-Probe Activity-Based Protein Profiling Reveals Site-Specific Differences in Protein Binding of EGFR-Directed Drugs

This study compares two EGFR-targeted drugs using ABPP to reveal site-specific binding differences and off-target effects at low concentrations.

Local structural flexibility drives oligomorphism in computationally designed protein assemblies

This study shows that structural flexibility in computationally designed protein assemblies leads to multiple architectures, expanding their functional possibilities.

Gene and protein sequence features augment HLA class I ligand predictions

The paper evaluates gene and protein sequence features as predictors of HLA class I ligand presentation, showing they improve predictions comparable to experimental gene expression data.

Direct mass spectrometry-based detection and antibody sequencing of Monoclonal Gammopathy of Undetermined Significance from patient serum - a case study.

This paper detects MGUS using LC-MS and determines M-protein sequences from serum, providing molecular detail for monoclonal gammopathies.

Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses

This study shows bispecific antibodies combine the neutralizing breadth and potency of parental antibodies to neutralize SARS-CoV and SARS-CoV-2 variants, including Omicron.

MRPS36 provides a missing link in the eukaryotic 2-oxoglutarate dehydrogenase complex for recruitment of E3 to the E2 core

The paper identifies MRPS36 as an essential component of the eukaryotic 2-oxoglutarate dehydrogenase complex, replacing the bacterial PSBD and providing structural insights into its organization.

Spectral Interferences Impede the High-Resolution Mass Analysis of Recombinant Adeno-Associated Viruses

The paper characterizes recombinant adeno-associated viruses (rAAVs) using native mass spectrometry, revealing spectral interferences caused by heterogeneity and charging behavior.

Thriving in the heat - Lysine acetylation stabilizes the quaternary structure of a Mega-Dalton hyperthermoactive PEP-synthase

The paper investigates how lysine acetylation stabilizes the structure of a hyperthermoactive PEP-synthase from Pyrococcus furious, revealing its role in maintaining function under extreme temperatures.

Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

The paper uses single-cell RNA sequencing to analyze neuroblastoma and identifies the NECTIN2-TIGIT axis as a potential target for immunotherapy.

Oxonium Ion-Guided Ion Mobility-Assisted Glycoproteomics on the timsTOF Pro

This paper introduces a method using ion mobility on the timsTOF Pro to separate glycopeptides from non-modified peptides, improving glycoproteomics analysis of complex samples.

Humans have distinct repertoires of IgA1

This study identifies two distinct structural populations of IgA1 in human serum and milk, with different clonal repertoires and origins.

IgG1 responses following SARS-CoV-2 infection are polyclonal and highly personalized, whereby each donor and each clone displays a distinct pattern of cross-reactivity against SARS-CoV-2 variants

The paper analyzes IgG1 clonal responses to SARS-CoV-2 variants in infected donors, finding unique and polyclonal antibody repertoires with varying cross-reactivity across variants.

Promoting Fc-Fc interactions between anti-capsular antibodies provides strong complement-dependent immune protection against Streptococcus pneumoniae

This paper shows that modifying anti-capsular antibodies to enhance hexamerization improves complement activation and immune protection against Streptococcus pneumoniae.

Chaperoning of the histone octamer by the acidic domain of DNA repair factor APLF

The paper shows that the acidic domain of APLF assembles histone octamers and deposits them onto DNA to form nucleosomes.

Soluble MAC is primarily released from MAC-resistant bacteria that potently convert complement component C5

The paper investigates how soluble MAC (sMAC) is formed during bacterial infections, finding that MAC-resistant bacteria convert C5 into C5b more efficiently and release sMAC, which can lyse bystander erythrocytes.

Assessment of genome packaging in AAVs using Orbitrap-based charge detection mass spectrometry

This paper introduces a method using Orbitrap-based charge detection mass spectrometry to rapidly and sensitively quantify AAV genome packaging, improving bioprocessing and drug development.

Single-embryo phosphoproteomics reveals the importance of intrinsic disorder in cell cycle dynamics

The paper uses single-embryo phosphoproteomics to show that phosphorylation of intrinsically disordered proteins by cell cycle kinases drives switch-like mitotic reorganization.

Probing Affinity, Avidity, Anti-Cooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

This study uses single particle mass analyses to examine antibody binding to the SARS-CoV-2 spike protein, revealing sub-stoichiometric binding and its effectiveness in blocking ACE2.

Frequency chasing of individual megadalton ions in an Orbitrap analyzer improves precision of analysis in single molecule mass spectrometry

This study improves mass spectrometry precision by tracking ion frequency drift in high-mass ions, achieving better resolution and sampling through desolvation correction.

Structural basis for how sMAC is packaged for clearance

The paper determines the structure of soluble membrane attack complex (sMAC) using cryoEM and XL-MS, revealing how clusterin inhibits its polymerization and how C9 is trapped in an intermediate conformation.

HAP40 orchestrates huntingtin structure for differential interaction with polyglutamine expanded exon 1

This study reveals how HAP40 orchestrates HTT structure, affecting its interaction with polyglutamine-expanded exon 1, providing insights into Huntington's disease mechanisms.

In-cell structures of a conserved supramolecular array at the mitochondria-cytoskeleton interface in mammalian sperm

The paper uses cryo-electron tomography to image mitochondria-cytoskeleton interfaces in mammalian sperm, revealing conserved supramolecular arrays composed of glycerol kinase-like proteins.

Adeno-associated virus capsid assembly is divergent and stochastic

This study reveals that AAV capsid assembly is highly stochastic and heterogeneous, with each capsid having a unique composition.

Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation

This study shows Staphylococcal protein A inhibits IgG hexamer formation, blocking complement activation, but IgG3 can still induce complement activation despite SpA.

Benefits of Collisional Cross Section Assisted Precursor Selection (caps-PASEF) for Cross-linking Mass Spectrometry

The paper demonstrates that ion mobility improves cross-linking mass spectrometry by separating mono-linked peptides from cross-linked peptide pairs, increasing detected cross-linked peptides by 50-70%.

Flexible regions in the molecular architecture of Human fibrin clots structurally resolved by XL-MS and integrative structural modeling

This study resolves the molecular architecture of human fibrin clots using XL-MS and integrative modeling, revealing structural details of key domains and their role in lateral aggregation and clot formation.

Resolving heterogeneous high-mass macromolecular machineries by Orbitrap-based single particle charge detection mass spectrometry

This paper demonstrates that Orbitrap-based single particle charge detection mass spectrometry can resolve high-mass heterogeneous biomolecular assemblies by accurately predicting charge states and masses.

PhoX - an IMAC-enrichable Crosslinking Reagent

The paper introduces PhoX, a crosslinking reagent that enhances detection of crosslinked peptides through IMAC enrichment, demonstrating improved efficiency and specificity in structural studies.

Functional diversification of hybridoma produced antibodies by CRISPR/HDR genomic engineering

This study presents a CRISPR/HDR platform to engineer hybridoma antibodies for diverse isotypes, formats, and species, enabling functional antibody diversification.

A system-wide approach to monitor responses to synergistic BRAF and EGFR inhibition in colorectal cancer cells

The paper investigates molecular responses to BRAF and EGFR inhibition in colorectal cancer cells, revealing metabolic shifts and MAPK pathway reactivation.