Max Perutz Labs

A validation framework for translating ethnomicrobiology into microbiome-enabled desert restoration

Microbiome-based dryland restoration is promising but weakly validated. We develop ethnomicrobiology, the study of how human communities manage microbial processes, as a discovery-and-validation framework. A structured evidence map of 42 systems shows food fermentation is most ma...

Druggable secondary sites in C-type lectin-like domains: Mechanistic insights and opportunities for chemical modulation

C-type lectins are pivotal orchestrators of immunity and homeostasis. However, developing potent small molecule modulators remains a significant challenge, as their primary binding sites are shallow and solvent-exposed. Recent biophysical and computational advancements have revea...

Ashwin and FAM98 paralogs define nuclear and cytoplasmic RNA ligase complexes for tRNA biogenesis

Abstract The tRNA ligase complex (tRNA-LC) seals tRNA exon halves in the nucleus during pre-tRNA splicing and XBP1 -mRNA exons in the cytoplasm as part of the unfolded protein response (UPR). This dual function requires the tRNA-LC to be either nuclear or cytoplasmic. Here, we re...

Structural framework for the assembly of the human tRNA ligase complex

Abstract In human cells, a subset of tRNA-encoding genes contain introns. These are removed by a spliceosome-independent pathway in which the tRNA splicing endonuclease complex catalyzes intron excision. The resulting exons are subsequently ligated by the tRNA-ligase complex (tRN...

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...

GH172 Difructose Dianhydride I Synthase: A Two‐Stepped Journey via Glycosylation and Cyclization Using QM/MM Metadynamics

ABSTRACT The difructose dianhydride I synthase/hydrolase catalyzes the reversible transformation of inulobiose into difructose dianhydride I, a component of caramel. The proposed reaction mechanism of such a transformation consists of a glycosylation step followed by a cyclizatio...

Loss of Twist impairs tentacle development and induces epithelial neoplasia in the sea anemone Nematostella vectensis.

Appendages are key features of the body plans of arthropods and vertebrates, yet little is known about appendage formation outside of bilaterians. Here, we investigate the molecular regulation underlying the formation of tentacles, the appendages in cnidarians. We find that the b...

A lipid transfer-dependent feedback loop activates ATG9A compartments in autophagy initiation

Abstract Autophagy degrades cellular material by sequestering it within autophagosomes, which form de novo from precursors called phagophores. Phagophore assembly and expansion require ATG9A-positive seed compartments, the lipid transfer protein ATG2A, and the class III phosphati...

Transposon end recognition and excision mechanisms of type I-F CRISPR-associated transposases

Abstract CRISPR-associated transposons (CASTs) are Tn7-like elements that have co-opted RNA-guided CRISPR effectors for targeted DNA insertion. CASTs have been adapted as genome editing tools for programmable, site-specific integration. Among them, the type I-F system from Ps e u...

Peripheral lysosomes recruit PLEKHG3 to focal adhesions and restrain protrusion dynamics

Lysosomes are dynamic organelles regulating metabolic signaling by recruiting cytosolic molecules to protein platforms on their limiting membrane. We used proximity labeling to define interactors and vicinal proteins of LAMTOR3, a component of the Ragulator scaffold that controls...