Welcome to Hannes!

Hannes has just started as a PhD student in our lab!


Harbrecht_Hannes

Posted in Uncategorized | Comments Off

Dr M. Madan Babu awarded Lister Research Prize

Congratulations to Madan to be awarded the prestigious Lister Research prize this year along with Melina Schuh, another LMB group leader. Madan’s Lister Research Prize has been awarded for his work on dynamics of tRNA abundance and the regulation of protein expression levels. He will deliver his Lister Prize Lecture at the awards ceremony on Friday 5th September 2014. Here is the detailed information as shown in the LMB website.

Posted in Uncategorized | Comments Off

Asymmetric mRNA localization contributes to fidelity and sensitivity of spatially localized systems

Although many proteins are localized after translation, asymmetric protein distribution is also achieved by translation after mRNA localization. Why are certain mRNA transported to a distal location and translated on-site? Here we undertake a systematic, genome-scale study of asymmetrically distributed protein and mRNA in mammalian cells. Our findings suggest that asymmetric protein distribution by mRNA localization enhances interaction fidelity and signaling sensitivity. Proteins synthesized at distal locations frequently contain intrinsically disordered segments. These regions are generally rich in assembly-promoting modules and are often regulated by post-translational modifications. Such proteins are tightly regulated but display distinct temporal dynamics upon stimulation with growth factors. Thus, proteins synthesized on-site may rapidly alter proteome composition and act as dynamically regulated scaffolds to promote the formation of reversible cellular assemblies. Our observations are consistent across multiple mammalian species, cell types and developmental stages, suggesting that localized translation is a recurring feature of cell signaling and regulation. The paper by Robert Weatheritt et al can be found here.

Posted in Uncategorized | Comments Off

A Million Peptide Motifs for the Molecular Biologist

A molecular description of functional modules in the cell is the focus of many high-throughput studies in the postgenomic era. A large portion of biomolecular interactions in virtually all cellular processes is mediated by compact interaction modules, referred to as peptide motifs. Such motifs are typically less than ten residues in length, occur within intrinsically disordered regions, and are recognized and/or posttranslationally modified by structured domains of the interacting partner. In this review, we suggest that there might be over a million instances of peptide motifs in the human proteome. While this staggering number suggests that peptide motifs are numerous and the most understudied functional module in the cell, it also holds great opportunities for new discoveries. The review can be found here.

Posted in Uncategorized | Comments Off

Welcome to Louis!

Louis is visiting us for three months as a summer student. A very warm welcome to him!

Posted in Uncategorized | Comments Off

Welcome to Daniel and Alexey!

Daniel and Alexey are our two new PhD students who started recently. A very warm welcome to both of them!


Estevez Prado_Daniel Alexey Morgunov

Posted in Uncategorized | Comments Off

Use of Host-like Peptide Motifs in Viral Proteins Is a Prevalent Strategy in Host-Virus Interactions

Viruses interact extensively with host proteins, but the mechanisms controlling these interactions are not well understood. We present a comprehensive analysis of eukaryotic linear motifs (ELMs) in 2,208 viral genomes and reveal that viruses exploit molecular mimicry of host-like ELMs to possibly assist in host-virus interactions. Using a statistical genomics approach, we identify a large number of potentially functional ELMs and observe that the occurrence of ELMs is often evolutionarily conserved but not uniform across virus families. Some viral proteins contain multiple types of ELMs, in striking similarity to complex regulatory modules in host proteins, suggesting that ELMs may act combinatorially to assist viral replication. Furthermore, a simple evolutionary model suggests that the inherent structural simplicity of ELMs often enables them to tolerate mutations and evolve quickly. Our findings suggest that ELMs may allow fast rewiring of host-virus interactions, which likely assists rapid viral evolution and adaptation to diverse environments. The paper can be found here.

Posted in Uncategorized | Comments Off

Controlling entropy to tune the functions of intrinsically disordered regions

Intrinsically disordered regions (IDRs) are fundamental units of protein function and regulation. Despite their inability to form a unique stable tertiary structure in isolation, many IDRs adopt a defined conformation upon binding and achieve their function through their interactions with other biomolecules. However, this requirement for IDR functionality seems to be at odds with the high entropic cost they must incur upon binding an interaction partner. How is this seeming paradox resolved? While increasing the enthalpy of binding is one approach to compensate for this entropic cost, growing evidence suggests that inherent features of IDRs, for instance repeating linear motifs, minimise the entropic cost of binding. Moreover, this control of entropic cost can be carefully modulated by a range of regulatory mechanisms, such as alternative splicing and post-translational modifications, which enable allosteric communication and rheostat-like tuning of IDR function. In that sense, the high entropic cost of IDR binding can be advantageous by providing tunability to protein function. In addition to biological regulatory mechanisms, modulation of entropy can also be controlled by environmental factors, such as changes in temperature, redox-potential and pH. These principles are extensively exploited by a number of organisms, including pathogens. They can also be utilised in bioengineering, synthetic biology and in pharmaceutical applications such as increasing bioavailability of protein therapeutics. The review by Tilman Flock, Robert J Weatheritt, Natasha S Latysheva and M Madan Babu can be found here.

Posted in Uncategorized | Comments Off

Classification of Intrinsically Disordered Regions and Proteins

The review by Robin van der Lee et al can be found here.

 

Posted in Uncategorized | Comments Off

Structural polymorphism in the N-terminal oligomerization domain of NPM1

Nucleophosmin (NPM1) is a multifunctional phospho-protein with critical roles in ribosome biogenesis, tumor suppression, and nucleolar stress response. Here we show that the N-terminal oligomerization domain of NPM1 (Npm-N) exhibits structural polymorphism by populating conformational states ranging from a highly ordered, folded pentamer to a highly disordered monomer. The monomer–pentamer equilibrium is modulated by posttranslational modification and protein binding. Phosphorylation drives the equilibrium in favor of monomeric forms, and this effect can be reversed by Npm-N binding to its interaction partners. We have identified a short, arginine-rich linear motif in NPM1 binding partners that mediates Npm-N oligomerization. We propose that the diverse functional repertoire associated with NPM1 is controlled through a regulated unfolding mechanism signaled through posttranslational modifications and intermolecular interactions. The paper with Marija Buljan et al can be found here.

Posted in Uncategorized | Comments Off