M. Madan Babu's Group

Molecular signatures of G-protein-coupled receptors published in Nature

madanm February 13, 2013 1:25 am

In this work, we objectively compare known structures and reveal key similarities and differences among diverse GPCRs. We identify a consensus structural scaffold of GPCRs that is constituted by a network of non-covalent contacts between residues on the transmembrane helices. By systematically analysing structures of the different receptor–ligand complexes, we identify a consensus ‘ligand-binding cradle’ that constitutes the bottom of the ligand-binding pocket within the TM bundle. Furthermore, our comparative study suggests that the third TM helix has a central role as a structural and functional hub. The paper can be found here and the press release by MRC can be found here. Our work was No. 1 in Nature’s top 10 downloaded articles in February 2013, featured in Nature’s GPCR focus section and mentioned in the cover page.

Network based approach to study DNA-DNA contacts published in Nucleic Acids Research

madanm November 21, 2012 4:12 pm

In this paper, we present a general statistical framework that is widely applicable to the analysis of genomic contact maps, irrespective of the data acquisition and normalization processes. Within this framework DNA–DNA contact data are represented as a complex network where DNA segments and contacts between them are denoted as nodes and edges, respectively. We also present a robust method for generating randomized contact networks that explicitly take into account the inherent 3D nature of the genome and serve as realistic null-models for unbiased statistical analyses. Our paper was chosen as a featured article by NAR. The paper by Kai Kruse et al can be found here.

Strategies to control functional and non-functional aggregation published in Cell Reports

madanm November 15, 2012 12:00 pm

Growing evidence suggests that aggregation-prone proteins are both harmful and functional for a cell. How do cellular systems balance the detrimental and beneficial effect of protein aggregation? In this work, we reveal that aggregation-prone proteins are subject to differential transcriptional, translational, and degradation control compared to nonaggregation-prone proteins, which leads to their decreased synthesis, low abundance, and high turnover. Genetic modulators that enhance the aggregation phenotype are enriched in genes that influence expression homeostasis. Moreover, genes encoding aggregation-prone proteins are more likely to be harmful when overexpressed. The trends are evolutionarily conserved and suggest a strategy whereby cellular mechanisms specifically modulate the availability of aggregation-prone proteins to (1) keep concentrations below the critical ones required for aggregation and (2) shift the equilibrium between the monomeric and oligomeric/aggregate form, as explained by Le Chatelier’s principle. This strategy may prevent formation of undesirable aggregates and keep functional assemblies/aggregates under control. The paper can be found here.

Perspective on Intrinsically Disordered Regions published in Science

madanm September 22, 2012 7:11 pm

In this perspective piece, we discuss the notion that disordered regions are largely passive is being actively challenged by the idea that they perform diverse functions. We also discuss how the synergy between structured and disordered regions expands the functional repertoires of proteins. You can read the Perspective here and an accompanying news article here.

Welcome to Balaji Santhanam!

madanm September 12, 2012 7:25 pm

Dr. Balaji Santhanam from Harvard University has just started as a new Senior Investigator Scientist at the LMB. A very warm welcome from all of us Balaji. We are looking forward to some very exciting discussions and science in the coming days.

NEWS & UPDATES

Molecular signatures of G-protein-coupled receptors published in Nature

Network based approach to study DNA-DNA contacts published in Nucleic Acids Research

Strategies to control functional and non-functional aggregation published in Cell Reports

Perspective on Intrinsically Disordered Regions published in Science

Welcome to Balaji Santhanam!

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