1.Quantitative proteome-based guidelines for intrinsic disorder characterization.
Vincent M1, Whidden M1, Schnell S2. Biophys Chem. 2016 Apr 5;213:6-16. doi: 10.1016/j.bpc.2016.03.005. [Epub ahead of print]
Intrinsically disordered proteins fail to adopt a stable three-dimensional structure under physiological conditions. It is now understood that many disordered proteins are not dysfunctional, but instead engage in numerous cellular processes, including signaling and regulation. Disorder characterization from amino acid sequence relies on computational disorder prediction algorithms. While numerous large-scale investigations of disorder have been performed using these algorithms, and have offered valuable insight regarding the prevalence of protein disorder in many organisms, critical proteome-based descriptive statistical guidelines that would enable the objective assessment of intrinsic disorder in a protein of interest remain to be established. Here we present a quantitative characterization of numerous disorder features using a rigorous non-parametric statistical approach, providing expected values and percentile cutoffs for each feature in ten eukaryotic proteomes.
2.Hemagglutinin of influenza A virus binds specifically to cell surface nucleolin and plays a role in virus internalization.
Chan CM1, Chu H1, Zhang AJ1, Leung LH2, Sze KH1, Kao RY1, Chik KK3, To KK1, Chan JF1, Chen H1, Jin DY4, Liu L2, Yuen KY5. Virology. 2016 Apr 13;494:78-88. doi: 10.1016/j.virol.2016.04.008. [Epub ahead of print]
The hemagglutinin (HA) protein of influenza A virus initiates cell entry by binding to sialic acids on target cells. In the current study, we demonstrated that in addition to sialic acids, influenza A/Puerto Rico/8/34 H1N1 (PR8) virus HA specifically binds to cell surface nucleolin (NCL). The interaction between HA and NCL was initially revealed with virus overlay protein binding assay (VOPBA) and subsequently verified with co-immunoprecipitation. Importantly, inhibiting cell surface NCL with NCL antibody, blocking PR8 viruses with purified NCL protein, or depleting endogenous NCL with siRNA all substantially reduced influenza virus internalization. We further demonstrated that NCL was a conserved cellular factor required for the entry of multiple influenza A viruses, including H1N1, H3N2, H5N1, and H7N9. Overall, our findings identified a novel role of NCL in influenza virus life cycle and established NCL as one of the host cell surface proteins for the entry of influenza A virus.
3.Ultra-trace graphene oxide in a water environment triggers Parkinson's disease-like symptoms and metabolic disturbance in zebrafish larvae.
Ren C1, Hu X2, Li X3, Zhou Q4. Biomaterials. 2016 Mar 31;93:83-94. doi: 10.1016/j.biomaterials.2016.03.036. [Epub ahead of print]
Over the past decade, the safety of nanomaterials has attracted attention due to their rapid development. The relevant health threat of these materials remains largely unknown, particularly at environmentally or biologically relevant ultra-trace concentrations. To address this, we first found that graphene oxide (GO, a carbon nanomaterial that receives extensive attention across various disciplines) at concentrations of 0.01 μg/L-1 μg/L induced Parkinson's disease-like symptoms in zebrafish larvae. In this model, zebrafish showed a loss of more than 90% of dopamine neurons, a 69-522% increase in Lewy bodies (α-synuclein and ubiquitin) and significantly disturbed locomotive activity. Moreover, it was also shown that GO was able to translocate from the water environment to the brain and localize to the nucleus of the diencephalon, thereby inducing structural and morphological damage in the mitochondria. Cell apoptosis and senescence were triggered via oxidative stress, as shown by the upregulation of caspase 8 and β-galactosidase.
