Max Planck Institute of Biophysics

PI3Kδ is selectively inhibited by roginolisib by stabilizing the C-terminal helix kα12

Abstract Phosphoinositide 3-kinases (PI3Ks) are major regulators of cell growth, proliferation and signalling, constituting key therapeutic targets in cancer, inflammation, and other diseases. Individual class I PI3K isoforms control key cellular functions, imposing the need to g...

Bayesian Learning of Distance Metrics Beyond RMSD for Biomolecule Alignment, Clustering, and Domain Identification

Abstract Root-mean-square deviation (RMSD) is the standard metric of structural comparison in molecular dynamics (MD) simulations. In its conventional form, RMSD assigns equal weight to all atoms regardless of mobility. Hence, flexible loops and disordered regions can dominate a...

Glaciers and low-DOC ecosystems as sites of microbial carbon production and consumption

Abstract Glacier-fed waters are commonly viewed as heterotrophic ecosystems fuelled by highly bioavailable dissolved organic carbon (DOC), yet this paradigm is largely based on melt-season observations and assumes that microbial DOC dynamics are dominated by consumption. We show...

Molecular mechanism of calcium inhibition in viral channelrhodopsins

Abstract Viral channelrhodopsins (VCR1s) are giant-virus-encoded light-gated channels permeable to monovalent and divalent cations, including Na + and Ca 2+ ions, and inhibited by millimolar Ca 2+ concentrations. Here, we combine X-ray crystallography, time-resolved UV-vis spectr...

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy

Abstract The Human ULK1 autophagy-initiating complex consists of ULK1, FIP200, and the HORMA domain heterodimer ATG13:ATG101. PI3P is essential to recruit ULK1C to membranes for ULK1, but ULK1C subunits do not contain PI3P-binding domains. Here we show that the ATG13:ATG101 dimer...

Characterization of Full‐Length Antibody Complexes Through HDX‐Mass Spectrometry Coupled With NMR Spectroscopy: New Insight Into Avelumab/PD‐L1 Interaction

ABSTRACT Recombinant biomacromolecules have significantly transformed pharmaceuticals, in particular monoclonal antibodies (mAbs) that target key areas in oncology, immunology, inflammation, and neurodegenerative diseases. Developing biotherapeutics requires a detailed understand...