Versatile modes of cellular regulation via cyclic dinucleotides

March 22nd, 2017 by Petya Violinova Krasteva

Nature Chemical Biology 13, 350 (2017). doi:10.1038/nchembio.2337

Authors: Petya Violinova Krasteva & Holger Sondermann

Signaling: Spatial regulation of axonal cAMP

March 22nd, 2017 by Pierre Vincent

Nature Chemical Biology 13, 348 (2017). doi:10.1038/nchembio.2339

Authors: Pierre Vincent & Liliana R Castro

In early-stage developing neurons, the cAMP–PKA (protein kinase A) signaling pathway is strongly inhibited. This negative control is later removed, unleashing cAMP–PKA signaling, particularly in distal axonal parts, thus allowing for axonal growth.

Protein folding: Illuminating chaperone activity

March 22nd, 2017 by Danny M Hatters

Nature Chemical Biology 13, 346 (2017). doi:10.1038/nchembio.2332

Author: Danny M Hatters

Pharmacological chaperones are small drugs that stabilize a protein's fold and are being developed to treat diseases arising from protein misfolding. A mathematical framework to model their activity in cells enables insight into their mechanism and capacity to rescue protein foldedness.

Simultaneous quantification of protein order and disorder

March 22nd, 2017 by Pietro Sormanni

Nature Chemical Biology 13, 339 (2017). doi:10.1038/nchembio.2331

Authors: Pietro Sormanni, Damiano Piovesan, Gabriella T Heller, Massimiliano Bonomi, Predrag Kukic, Carlo Camilloni, Monika Fuxreiter, Zsuzsanna Dosztanyi, Rohit V Pappu, M Madan Babu, Sonia Longhi, Peter Tompa, A Keith Dunker, Vladimir N Uversky, Silvio C E Tosatto & Michele Vendruscolo

Nuclear magnetic resonance spectroscopy is transforming our views of proteins by revealing how their structures and dynamics are closely intertwined to underlie their functions and interactions. Compelling representations of proteins as statistical ensembles are uncovering the presence and biological relevance of conformationally heterogeneous states, thus gradually making it possible to go beyond the dichotomy between order and disorder through more quantitative descriptions that span the continuum between them.

The direct role of selenocysteine in [NiFeSe] hydrogenase maturation and catalysis

March 20th, 2017 by Marta C Marques

Nature Chemical Biology 13, 544 (2017). doi:10.1038/nchembio.2335

Authors: Marta C Marques, Cristina Tapia, Oscar Gutiérrez-Sanz, Ana Raquel Ramos, Kimberly L Keller, Judy D Wall, Antonio L De Lacey, Pedro M Matias & Inês A C Pereira

  • Posted in Nat Chem Biol, Publications
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Metagenomic discovery of polybrominated diphenyl ether biosynthesis by marine sponges

March 20th, 2017 by Vinayak Agarwal

Nature Chemical Biology 13, 537 (2017). doi:10.1038/nchembio.2330

Authors: Vinayak Agarwal, Jessica M Blanton, Sheila Podell, Arnaud Taton, Michelle A Schorn, Julia Busch, Zhenjian Lin, Eric W Schmidt, Paul R Jensen, Valerie J Paul, Jason S Biggs, James W Golden, Eric E Allen & Bradley S Moore

  • Posted in Nat Chem Biol, Publications
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A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation

March 20th, 2017 by Kai Papenfort

Nature Chemical Biology 13, 551 (2017). doi:10.1038/nchembio.2336

Authors: Kai Papenfort, Justin E Silpe, Kelsey R Schramma, Jian-Ping Cong, Mohammad R Seyedsayamdost & Bonnie L Bassler

  • Posted in Nat Chem Biol, Publications
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The RecJ2 Protein in the Thermophilic Archaeon Thermoplasma acidophilum Is a 3′ 5′ Exonuclease and Associates with a DNA Replication Complex [Microbiology]

March 16th, 2017 by Hiromi Ogino, Sonoko Ishino, Daisuke Kohda, Yoshizumi Ishino

RecJ/cell division cycle 45 (Cdc45) proteins are widely conserved in the three domains of life, i.e., in Bacteria, Eukarya and Archaea. Bacterial RecJ is a 5′ 3′ exonuclease and functions in DNA repair pathways, while using its 5′ 3′ exonuclease activity. Eukaryotic Cdc45 has no identified enzymatic activity, but participates in the CMG complex so named because it is composed of Cdc45, minichromosome maintenance protein complex (MCM) proteins 2-7, and GINS complex proteins (Sld5, Psf11 to 3). Eukaryotic Cdc45 and bacterial/archaeal RecJ share similar amino acid sequences and are considered functional counterparts. In Archaea, a RecJ homolog in Thermococcus kodakarensis was shown to associate with GINS and accelerate its nuclease activity and was therefore designated GAN (GINS-associated nuclease); however, to date, no archaeal RecJ MCM GINS complex has been isolated. The thermophilic archaeon Thermoplasma acidophilum has two RecJ like proteins, designated TaRecJ1 and TaRecJ2. TaRecJ1 exhibited DNA-specific 5′ 3′exonuclease activity, while TaRecJ2 had 3′ 5′ exonuclease activity and preferred RNA over DNA. TaRecJ2, but not TaRecJ1, formed a stable complex with TaGINS in a 2:1 molar ratio. Furthermore, the TaRecJ2-TaGINS complex stimulated activity of TaMCM helicase in vitro, and the TaRecJ2-TaMCM-TaGINS complex was also observed in vivo. However, TaRecJ2 did not interact with TaMCM directly and was not required for the helicase activation in vitro. These findings suggest that the function of archaeal RecJ in DNA replication evolved divergently from Cdc45 despite conservation of the CMG-like complex formation between Archaea and Eukarya.
  • Posted in Journal of Biological Chemistry, Publications
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Adjacent channelrhodopsin-2 residues within transmembranes 2 and 7 regulate cation selectivity and distribution of the two open states [Membrane Biology]

March 16th, 2017 by Ryan Richards, Robert E. Dempski

Channelrhodopsin-2 (ChR2) is a light-activated channel that can conduct cations of multiple valencies down the electrochemical gradient. Under continuous light exposure, ChR2 transitions from a high conducting open state (O1) to a low conducting open state (O2) with differing ion selectivity. The molecular basis for the O1 to O2 transition and how ChR2 modulates selectivity between states is currently unresolved. To this end, we used steered molecular dynamics, electrophysiology, and kinetic modeling to identify residues that contribute to gating and selectivity in discrete open states. Analysis of steered molecular dynamics experiments identified three transmembrane residues (V86, K93 and N258) that form a putative barrier to ion translocation. Kinetic modeling of photocurrents generated from ChR2 proteins with conservative mutations at these positions demonstrated that these residues contribute to cation selectivity (V86 and N258), the transition between the two open states (V86), open channel stability, and the hydrogen-bonding network (K93I and K93N). These results suggest that this approach can be used to identify residues that contribute to the open state transitions and the discrete ion selectivity within these states. With the rise of ChR2 use in optogenetics, it will be critical to identify residues that contribute to O1 or O2 selectivity and gating to minimize undesirable effects.
  • Posted in Journal of Biological Chemistry, Publications
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A Secretion-Amplification Role for Salmonella enterica Translocon Protein SipD

March 16th, 2017 by Anum Azam Glasgow, Han Teng Wong and Danielle Tullman-Ercek

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.6b00335