ACS 253rd National Meeting News

October 14th, 2016 by Šileikyte, J., Blachly–Dyson, E., Sewell, R., Carpi, A., Menabo, R., Di Lisa, F., Ricchelli, F., Bernardi, P., Forte, M.

  1. Abstract deadline Oct. 31, 2016 for Spring 2017 meeting in San Francisco

In addition to poster sessions, there will be oral sessions for contributed papers from Graduate students and postdocs, Early Career Investigators and (New!) Mid Career investigators.

Abstract submissions at https://callforpapers.acs.org/sanfran2017/BIOL

  1. Travel Award deadline Jan. 15, 2017 for the Spring 2017 meeting.

Application and information at http://www.divbiolchem.org/awards/travel-awards/

  1. (New!) Symposium proposals for Spring 2018 meeting deadline Feb. 15, 2017

We are soliciting proposals for symposia for the 2018 meetings.  Download the application here.

  1. Spring 2017 Program Preview
  • Ronald Breslow Award for Achievement in Biomimetic Chemistry: Symposium in honor of Benjamin G. Davis
  • ACS Award in Pure Chemistry: Symposium in honor of Neal K. Devaraj
  • Goodman Award: Symposium in honor of Jennifer Doudna
  • ACS Chemical Biology Award Symposium (organizer L. Kiessling)
  • Nucleic Acid Therapeutics: mechanisms  and applications (organizer M. Manoharan)
  • Self-assembly of small molecules in the cellular milieu (organizer B. Xu)
  • Metalloprotein-initiated Signaling Transduction Response to Redox Stress (organizer A. Liu)
  • Chemical Probes for Bacterial Imaging (organizer E. Carlson)
  • Chemical Epigenetics (organizer D. Fujimori)

Crotonic Acid Blocks the Gloeobacter Ligand-Gated Ion Channel (GLIC) via the Extracellular Domain

October 14th, 2016 by Mona A. Alqazzaz, Kerry L. Price and Sarah C. R. Lummis

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.6b00531

The phosphoinositide 3-kinase regulates retrograde trafficking of the iron permease CgFtr1 and iron homeostasis in Candida glabrata [Microbiology]

October 11th, 2016 by Sharma, V., Purushotham, R., Kaur, R.

The phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol and produces PI3P, has been implicated in protein trafficking, intracellular survival and virulence in the pathogenic yeast Candida glabrata. Here, we demonstrate PI3-kinase (CgVps34) to be essential for maintenance of cellular iron homeostasis. We examine how CgVps34 regulates the fundamental process of iron acquisition, and underscore its function in vesicular trafficking as a central determinant. RNA-sequencing analysis revealed iron homeostasis genes to be differentially expressed upon CgVps34 disruption. Consistently, the Cgvps34Δ mutant displayed growth attenuation in low- and high-iron media, increased intracellular iron content, elevated mitochondrial aconitase activity, impaired biofilm formation and extenuated mouse organ colonization potential. Further, we demonstrate for the first time that C. glabrata cells respond to iron-limitation by expressing the iron permease CgFtr1 primarily on the cell membrane, and to iron-excess via internalization of the plasma membrane-localized CgFtr1 to the vacuole. Our data show that CgVps34 is essential for the latter process. We also report that macrophage-internalized C. glabrata cells express CgFtr1 on the cell membrane indicative of an iron-restricted macrophage internal milieu, and Cgvps34Δ cells display better survival in iron-enriched medium-cultured macrophages. Overall, our data reveal the centrality of PI3K signaling in iron metabolism and host colonization.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on The phosphoinositide 3-kinase regulates retrograde trafficking of the iron permease CgFtr1 and iron homeostasis in Candida glabrata [Microbiology]

Cdc24 is essential for long-range end resection in the repair of dsDNA breaks [Metabolism]

October 11th, 2016 by Zhang, H., Hua, Y., Li, R., Kong, D.

Double-stranded DNA breaks (DSBs) are highly detrimental DNA lesions, which may be repaired by the homologous recombination-mediated repair pathway. The 5 prime to 3 prime direction of long-range end resection on one DNA strand, in which 3 prime-single-strand DNA overhangs are created from broken DNA ends, is an essential step in this pathway. Dna2 has been demonstrated as an essential nuclease in this event, but the molecular mechanism how Dna2 is recruited to DNA break sites in vivo is not elucidated. In this study, a novel recombination factor called Cdc24 was identified in fission yeast. We demonstrated that Cdc24 localizes to DNA break sites during the repair of DNA breaks and is an essential factor for long-range end resection. We also determined that Cdc24 plays a direct role in recruiting Dna2 to DNA break sites through its interaction with Dna2 and replication protein A (RPA). Further, this study revealed that RPA acts as a foundation in assembling the machinery for long-range end resection by its essential role in recruiting Cdc24 and Dna2 to DNA break sites. These results define Cdc24 as an essential factor for long-range end resection in the repair of DSBs, opening the door for further investigations into the enzymes involved in long-range end resection for DSB repair.

Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection

October 10th, 2016 by Gahl Levy

Nature Chemical Biology 12, 1037 (2016). doi:10.1038/nchembio.2193

Authors: Gahl Levy, Naomi Habib, Maria Angela Guzzardi, Daniel Kitsberg, David Bomze, Elishai Ezra, Basak E Uygun, Korkut Uygun, Martin Trippler, Joerg F Schlaak, Oren Shibolet, Ella H Sklan, Merav Cohen, Joerg Timm, Nir Friedman & Yaakov Nahmias

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection

Competing charge transfer pathways at the photosystem II–electrode interface

October 10th, 2016 by Jenny Z Zhang

Nature Chemical Biology 12, 1046 (2016). doi:10.1038/nchembio.2192

Authors: Jenny Z Zhang, Katarzyna P Sokol, Nicholas Paul, Elisabet Romero, Rienk van Grondelle & Erwin Reisner

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Competing charge transfer pathways at the photosystem II–electrode interface

A photoactivatable Cre–loxP recombination system for optogenetic genome engineering

October 10th, 2016 by Fuun Kawano

Nature Chemical Biology 12, 1059 (2016). doi:10.1038/nchembio.2205

Authors: Fuun Kawano, Risako Okazaki, Masayuki Yazawa & Moritoshi Sato

  • Posted in Nat Chem Biol, Publications
  • Comments Off on A photoactivatable Cre–loxP recombination system for optogenetic genome engineering

Serine is a new target residue for endogenous ADP-ribosylation on histones

October 10th, 2016 by Orsolya Leidecker

Nature Chemical Biology 12, 998 (2016). doi:10.1038/nchembio.2180

Authors: Orsolya Leidecker, Juan José Bonfiglio, Thomas Colby, Qi Zhang, Ilian Atanassov, Roko Zaja, Luca Palazzo, Anna Stockum, Ivan Ahel & Ivan Matic

ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and quantification of ADPr sites on histones. We have identified 12 unique ADPr sites in human osteosarcoma cells and report serine ADPr as a new type of histone mark that responds to DNA damage.

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Serine is a new target residue for endogenous ADP-ribosylation on histones

SF2312 is a natural phosphonate inhibitor of enolase

October 10th, 2016 by Paul G Leonard

Nature Chemical Biology 12, 1053 (2016). doi:10.1038/nchembio.2195

Authors: Paul G Leonard, Nikunj Satani, David Maxwell, Yu-Hsi Lin, Naima Hammoudi, Zhenghong Peng, Federica Pisaneschi, Todd M Link, Gilbert R Lee, Duoli Sun, Basvoju A Bhanu Prasad, Maria Emilia Di Francesco, Barbara Czako, John M Asara, Y Alan Wang, William Bornmann, Ronald A DePinho & Florian L Muller

Bipartite Role of Hsp90 Keeps CRAF Kinase Poised for Activation [Protein Structure and Folding]

October 5th, 2016 by Mitra, S., Ghosh, B., Gayen, N., Roy, J., Mandal, A. K.

CRAF kinase maintains cell viability, growth and proliferation by participating in MAPK pathway. Unlike BRAF, CRAF requires continuous chaperoning by Hsp90 to retain MAPK signaling. But, the reason behind the continuous association of Hsp90 with CRAF is still elusive. In this study, we have identified the bipartite role of Hsp90 in chaperoning CRAF kinase. Hsp90 facilitates Ser-621 phosphorylation of CRAF and prevents the kinase from degradation. Co-chaperone Cdc37 assists in this phosphorylation event. However, after folding the stability of the kinase becomes insensitive to Hsp90 inhibition, although the physical association between Hsp90 and CRAF remains intact. We observe that over-expression of Hsp90 stimulates MAPK signaling by activating CRAF. The interaction between Hsp90 and CRAF is substantially increased under elevated level of cellular Hsp90 and in presence of either active Ras (RasV12) or EGF. Surprisingly, enhanced binding of Hsp90 to CRAF occurs prior to the Ras-CRAF association and facilitates actin recruitment to CRAF for efficient Ras-CRAF interaction, which is independent of Hsp90s ATPase activity. However, monomeric CRAF (CRAF R401H) shows abrogated interaction with both Hsp90 and actin, thereby affecting Hsp90-dependent CRAF activation. This finding suggests that stringent assemblage of Hsp90 keeps CRAF kinase equipped for participating in MAPK pathway. Thus, the role of Hsp90 in CRAF maturation and activation acts as a limiting factor to maintain the function of a strong client like CRAF kinase.