Read about some of the latest publications from the Department.
Drosophila Syncrip modulates the expression of mRNAs encoding key synaptic proteins required for morphology at the neuromuscular junction. McDermott SM, Yang L, Halstead JM, Hamilton RS, Meignin C and Davis I. RNA 2014 20:1593-606
Localised mRNA translation is thought to play a key role in synaptic plasticity, but the identity of the transcripts and the molecular mechanism underlying their function are still poorly understood. This paper describes how Syncrip, a regulator of localised translation in the Drosophila oocyte and a component of mammalian neuronal mRNA granules, is also expressed in the Drosophila larval neuromuscular junction where it associates with a number of mRNAs encoding proteins with key synaptic functions. The researchers propose that Syncrip acts as a modulator of synaptic plasticity by regulating the translation of these key mRNAs.
Agonist and Antagonist Binding in Human Glycine Receptors. Yu R, Hurdiss E, Greiner T, Lape R Sivilotti L and Biggin PC. Biochemistry, 2014, 53 (38), 6041-6051
This paper describes the construction of a model of the human glycine receptor (hGlyR) and its validation against previously reported mutagenesis data. hGlyRs are particularly amenable to single-channel recordings, making them a model experimental system for understanding the larger superfamily of Cys-loop receptors to which they belong. However, the ability to investigate agonist binding and efficacy is hampered by the lack of a high-resolution structure for the complete hGlyR. Modeling is therefore needed to provide the physical framework on which to interpret single-channel data. The researchers used molecular dynamics to refine the model of the hGlyR and explore binding of both an agonist and an antagonist. The model shows excellent agreement with previous data but also suggests some unique features.
Lipid clustering correlates with membrane curvature as revealed by molecular simulations of complex lipid bilayers. Koldsoe H, Shorthouse D, Hélie J and Sansom MSP. PloS Comput Biol. Oct 2014; 10(10): e1003911
Cell membranes play important roles both in shielding the cell interior from the surrounding environment and in cell function through their lipid components influencing processes such as cell signaling. In this paper, the researchers use molecular dynamics simulations to explore the behaviour of biologically realistic membrane models. The simulations reveal nanoscale clustering of lipid molecules, which may be coupled to both fluctuation in local membrane geometry (membrane curvature) and to interactions with proteins.
Transcription mediated insulation and interference direct gene cluster expression switches. Nguyen T, Fischl H, Howe FS, Woloszczuk, Barros AS, Xu Z, Brown D, Murray SC, Haenni S, Halstead JM, O'Connor L, Shipkovenska G, Steinmetz LM and Mellor J. eLife 2014;10.7554/eLife.03635
In yeast, the activity of many genes is linked to the activity of their immediate neighbours and also to changes in environmental conditions, indicative of regulation of expression by switches. Nguyen et. al. investigated these mechanisms by engineering start and stop signals at a neighbouring pair of genes called HMS2 and BAT2 in yeast. When one gene is switched on, the other is switched off, and which gene is active depends upon the diet of the yeast cells. In addition, a gene on the antisense DNA strand opposite to HMS2 affects the transcription of these genes. The researchers show that the transcription process itself makes up part of a switch that controls the expression of several genes on both the sense and antisense strands of the double helix. This may explain how more complex gene networks are activated in response to changes in the environment.
MapZ marks the division sites and positions FtsZ-rings in Streptococcus pneumonia. Fleurie A, Lesterlin C, Manuse S, Zhao C, Cluzel C, Lavergne, J-P, Franz-Wachtel M, Macek B, Combet C, Kuru E, VanNieuwenhze MS, Brun YV, Sherratt D and Grangeassa C. Nature 516, 259-262 (11 December 2014)
This paper describes a new mechanism used by the human pathogen Streptococcus pneumonia for accurate identification of the division site and placement of the cell division machinery. In many bacteria, this process is controlled by the Min system which ensures that the ring formed by the highly conserved tubulin homologue FtsZ locates precisely at the mid-cell. The researchers show that in pneumococcus a novel factor locates at the division site before FtsZ and guides septum positioning. The work illustrates that nature has evolved a diversity of cell division mechanisms.
Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor. Lane-Serff H, MacGregor P, Lowe E, Carrington M and Higgins M. December 12 2014. eLife 2014;10.7554/eLife.05553
The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. This paper reports the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb). Lateral mobility of the anchored receptor and a kink in the receptor allow two receptors to simultaneously bind one HpHb dimer. The structure reveals the molecular basis for HpHb and innate immunity factor uptake by trypanosomes, and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface.
And already covered on the website:
Crystal Structure of the Bacillus subtilis Phosphodiesterase PhoD Reveals an Iron and Calcium-Containing Active Site. Rodriquez, F, Lillington, J, Johnson, S, Timmel, CG, Lea, SM and Berks, B. Journal of Biological Chemistry (2014) 289:30889-30899
Popp F, Armitage JP and Schuler D. Polarity of bacterial magnetotaxis is controlled by aerotaxis through a common sensory pathway. Nature Communications (2014). doi:10.1038/ncomms6398
Closing the cohesin ring: structure and function of its Smc3-kleisin interface.' Gligoris, TG, Scheinost, JC, Burmann, F, Petela, N, Chan, K-L, Uluocak, P, Beckouet, F, Gruber, S, Nasmyth, K and Löwe, J. Science (2014) Vol. 346 no. 6212 p963-967
Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters. Lyons JA, Parker JL, Solcan N, Brinth A, Li D, STA Shah, Caffrey M and Newstead S. EMBO reports( 2014) 15, 886-89
Thermodynamic evidence for a dual transport mechanism in a POT peptide transporter. Parker JL, Mindell JA and Newstead S. eLife 2014;3:e04273