Chemical Ligand Space of Cereblon.

The protein cereblon serves as a substrate receptor of a ubiquitin ligase complex that can be tuned toward different target proteins by cereblon-binding agents. This approach to targeted protein degradation is exploited in different clinical settings and has sparked the development of a growing number of thalidomide derivatives. Here, we probe the chemical space of cereblon binding beyond such derivatives and work out a simple set of chemical requirements, delineating the metaclass of cereblon effectors.

Characterization of MCU-Binding Proteins MCUR1 and CCDC90B - Representatives of a Protein Family Conserved in Prokaryotes and Eukaryotic Organelles.

Membrane-bound coiled-coil proteins are important mediators of signaling, fusion, and scaffolding. Here, we delineate a heterogeneous group of trimeric membrane-anchored proteins in prokaryotes and eukaryotic organelles with a characteristic head-neck-stalk-anchor architecture, in which a membrane-anchored coiled-coil stalk projects an N-terminal head domain via a β-layer neck. Based on sequence analysis, we identify different types of head domains and determine crystal structures of two representatives, the archaeal protein Kcr-0859 and the human CCDC90B, which possesses the most widespread head type.

A FRET-Based Assay for the Identification and Characterization of Cereblon Ligands.

Cereblon serves as an ubiquitin ligase substrate receptor that can be tuned toward different target proteins by various cereblon-binding agents. This offers one of the most promising avenues for targeted protein degradation in cancer therapy, but cereblon binding can also mediate teratogenic effects. We present an effective assay that is suited for high-throughput screening of compound libraries for off-target cereblon interactions but also can guide lead optimization and rational design of novel cereblon effector molecules.

Your personalized protein structure: Andrei N. Lupas fused to GCN4 adaptors.

This work presents a protein structure that has been designed purely for aesthetic reasons, symbolizing decades of coiled-coil research and praising its most fundamental model system, the GCN4 leucine zipper. The GCN4 leucine zipper is a highly stable coiled coil which can be tuned to adopt different oligomeric states via mutation of its core residues. For these reasons it is used in structural studies as a stabilizing fusion adaptor.

Complete fiber structures of complex trimeric autotransporter adhesins conserved in enterobacteria.

Trimeric autotransporter adhesins (TAAs) are modular, highly repetitive surface proteins that mediate adhesion to host cells in a broad range of Gram-negative pathogens. Although their sizes may differ by more than one order of magnitude, they all follow the same basic head-stalk-anchor architecture, where the head mediates adhesion and autoagglutination, the stalk projects the head from the bacterial surface, and the anchor provides the export function and attaches the adhesin to the bacterial outer membrane after export is complete. In complex adhesins, head and stalk domains may alternate several times before the anchor is reached.

Comprehensive mutation identification in an evolved bacterial cooperator and its cheating ancestor.

Precise characterization of the mutation histories of evolutionary lineages is crucial for understanding the evolutionary process, yet mutation identification has been constrained by traditional techniques. We sought to identify all accumulated mutations in an experimentally evolved lineage of the cooperative bacterium Myxococcus xanthus, which constructs fruiting bodies by a process of social multicellular development in response to starvation. This lineage had undergone two major transitions in social phenotype: from an ancestral cooperator to a socially defective cheater, and from the cheater to a competitively dominant cooperator that re-evolved social and developmental proficiency.

Glial and neuronal regulation of the lipid carrier R-FABP.

Neuroembryogenesis critically depends on signaling molecules that modulate cell proliferation, differentiation, and the formation of neural networks. In an attempt to identify potential morphogenetic active components that are distributed in a graded fashion in the developing nervous system, we generated substraction libraries of the embryonic nasal and temporal chick retina. Selected clones were analyzed by sequencing, Northern and Western blotting, in situ hybridization, and immunocytochemistry.