Volume 15 Issue 10, October 2019

Volume 15 Issue 10

Pacing metabolism

A metabolic tracing strategy was used for efficient determination of glycolytic thermodynamics revealing near-equilibrium glycolytic steps. The flow of sand represents glycolytic flux, with the narrowing of the hourglass depicting a thermodynamic bottleneck. The colors of the molecules represent the extent of deuterium labeling.

See Park et al.

Image: Eddie Rath, Meredith Fields, and Junyoung Park. Cover Design: Erin Dewalt

Research Highlights

News & Views

  • News & Views |

    A comprehensive genetic screen reveals new cellular trafficking factors and linker-dependent requirements for antibody–drug conjugate (ADC) cytotoxicity. These new insights may guide the design of optimized ADCs.

    • Heather A. Van Epps
    •  & Peter D. Senter
  • News & Views |

    A new sugar-based cysteine-reactive probe, combined with competitive activity-based protein profiling (ABPP), enables site-centric target deconvolution of itaconate in native proteomes, shedding light on a novel mechanism of action for this important immunoregulatory metabolite in inflammatory macrophages.

    • Jing Yang

Perspectives

  • Perspective |

    This Perspective summarizes recent discoveries that have laid the foundation for targeted degradation therapeutics and discusses the current state of understanding and consideration involved in developing these protein degraders.

    • Philip P. Chamberlain
    •  & Lawrence G. Hamann

Brief Communications

  • Brief Communication |

    The topology of homodimeric membrane protein EmrE is dynamic and includes unassisted flipping of an N-terminal helix in and out of the membrane long after co-translational insertion. Dimerization locks the helix to limit topological dynamics.

    • Maximilian Seurig
    • , Moira Ek
    • , Gunnar von Heijne
    •  & Nir Fluman

Articles

  • Article |

    A series of genome-wide and targeted CRISPR screens uncovered regulators of antibody–drug conjugate (ADC) toxicity. Depletion of sialic acids was found to enhance ADC lysosomal delivery, in part by reducing ADC recycling.

    • C. Kimberly Tsui
    • , Robyn M. Barfield
    • , Curt R. Fischer
    • , David W. Morgens
    • , Amy Li
    • , Benjamin A. H. Smith
    • , Melissa Anne Gray
    • , Carolyn R. Bertozzi
    • , David Rabuka
    •  & Michael C. Bassik
  • Article |

    Structural and biochemical characterization of the spirochaete flagellar hook protein FlgE reveals how cysteine and lysine residues spontaneously react to form an interdomain lysinoalanine crosslink without the involvement of additional enzymes.

    • Michael J. Lynch
    • , Michael Miller
    • , Milinda James
    • , Sheng Zhang
    • , Kai Zhang
    • , Chunhao Li
    • , Nyles W. Charon
    •  & Brian R. Crane
  • Article |

    An in vitro method was developed to screen mRNA sites for psedouridine modification by specific pseudouridylating enzymes and identify an RNA structural motif for Pus1, which can be used to predict new pseudouridylated mRNA targets in vivo.

    • Thomas M. Carlile
    • , Nicole M. Martinez
    • , Cassandra Schaening
    • , Amanda Su
    • , Tristan A. Bell
    • , Boris Zinshteyn
    •  & Wendy V. Gilbert
  • Article |

    Cholesterol can function as both a substrate and an inhibitor of the Hedgehog receptor Patched. Structural analysis and molecular dynamics simulations reveal that cholesterol inhibits Patched by inserting into its extracellular domain

    • Amalie F. Rudolf
    • , Maia Kinnebrew
    • , Christiane Kowatsch
    • , T. Bertie Ansell
    • , Kamel El Omari
    • , Benjamin Bishop
    • , Els Pardon
    • , Rebekka A. Schwab
    • , Tomas Malinauskas
    • , Mingxing Qian
    • , Ramona Duman
    • , Douglas F. Covey
    • , Jan Steyaert
    • , Armin Wagner
    • , Mark S. P. Sansom
    • , Rajat Rohatgi
    •  & Christian Siebold
  • Article |

    Using a thiol-reactive probe, chemoproteomic profiling of cysteine targets of itaconate reveals the covalent modification of glycolytic enzymes, impairing glycolytic flux and contributing to attenuation of the inflammatory response in macrophages.

    • Wei Qin
    • , Ke Qin
    • , Yanling Zhang
    • , Wentong Jia
    • , Ying Chen
    • , Bo Cheng
    • , Linghang Peng
    • , Nan Chen
    • , Yuan Liu
    • , Wen Zhou
    • , Yan-Ling Wang
    • , Xing Chen
    •  & Chu Wang
  • Article |

    KAT2A acetylates histone variant H2A.Z to regulate transactivation of XPC and RAR positively regulated genes. The DNA repair complex XPC–RAD23–CEN2 interacts with H2A.Z and KAT2A to license the latter’s histone acetyltransferase activity.

    • M. Semer
    • , B. Bidon
    • , A. Larnicol
    • , G. Caliskan
    • , P. Catez
    • , J. M. Egly
    • , F. Coin
    •  & N. Le May
  • Article |

    A 2H and 13C tracing strategy was used for efficient determination of glycolytic thermodynamics, revealing near-equilibrium glycolytic steps enabling rapid flux adaptation and, in Clostridium cellulolyticum, enhanced ATP yield.

    • Junyoung O. Park
    • , Lukas B. Tanner
    • , Monica H. Wei
    • , Daven B. Khana
    • , Tyler B. Jacobson
    • , Zheyun Zhang
    • , Sara A. Rubin
    • , Sophia Hsin-Jung Li
    • , Meytal B. Higgins
    • , David M. Stevenson
    • , Daniel Amador-Noguez
    •  & Joshua D. Rabinowitz
  • Article |

    Structural characterization of the amino-acid-modifying radical halogenase BesD and identification of new members of this protein family provides insight into the enzymatic mechanism and enables biocatalytic production of halogenated amino acids.

    • Monica E. Neugebauer
    • , Kiera H. Sumida
    • , Jeffrey G. Pelton
    • , Jonathan L. McMurry
    • , Jorge A. Marchand
    •  & Michelle C. Y. Chang
  • Article |

    Encapsulation of engineered bacteria in environmentally responsive materials enables on-demand protein production coupled to downstream processes such as protein purification, on-chip enzyme kinetics and metabolic production of fatty acids.

    • Zhuojun Dai
    • , Anna J. Lee
    • , Stefan Roberts
    • , Tatyana A. Sysoeva
    • , Shuqiang Huang
    • , Michael Dzuricky
    • , Xiaoyu Yang
    • , Xi Zhang
    • , Zihe Liu
    • , Ashutosh Chilkoti
    •  & Lingchong You

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