Volume 9 Issue 6, June 2013

On 2 April 2013, Amy L. Davidson lost her battle against thyroid cancer. The membrane transport field has lost one of its best biochemists and a superb mechanistic thinker. Amy devoted her career to uncovering the secrets of the maltose transporter, a prototype of a large protein family called ATP-binding cassette (ABC) transporters.

The synergistic action of cellulases is critical for the effective saccharification of cellulosic biomass, but the details of this cooperation remain poorly understood. Quantitative analysis at the level of single molecules now unveils a form of 'work sharing' among cellulolytic enzymes based on different adsorption specificities of their carbohydrate-binding modules.

BCL-X_L and other anti-apoptotic BCL-2 family proteins serve as guardians of cellular survival. A new selective small-molecule inhibitor of BCL-X_L is developed to promote apoptosis in cancers that are addicted to BCL-X_L.

PreQ₁, a metabolic precursor of the modified tRNA nucleotide queuosine, regulates expression of queuosine biosynthetic genes via two distinct classes of preQ₁ riboswitch. Biochemical studies and the first X-ray crystal structure of a class II preQ₁ riboswitch reveal how preQ₁ recognizes this RNA motif and how it may regulate translation of downstream genes.

The use of PALM imaging to quantify enzyme localization on technically challenging heterogeneous substrates yields a new directionally dependent metric for describing substrate specificity, the application of which explains synergy between carbohydrate-binding domains from diverse cellulases.

DNA origami has shown that principles of molecular recognition can be used to reshape biomolecules into nonphysiological forms. The design and synthesis of a continuous, 12-helix polypeptide that spontaneously self-assembles into a defined tetrahedron now demonstrates that protein structures can be similarly manipulated.

N-linked glycosylation in archaea has generally been assumed to follow the logic determined for bacterial and eukaryotic pathways. Biochemical investigations of the process in Methanococcus voltae now allow the functional assignment of three enzymes that generate and use an unusual monophosphate intermediate, drawing distinctions between domains of life.

Structure-based design of RARα antagonists leads to compounds that can selectively upregulate chaperone-mediated autophagy (CMA), yielding the first chemically tractable target for regulating CMA in cells.

The 20° tilt angle of β-strands within the transmembrane β-barrel formed by bacterial perfingolysin O reveals how helices in adjacent monomers select the proper hydrogen-bonding partner during assembly.

A high-throughput chemical screen followed by structure-guided chemical design leads to the first potent and selective small-molecule BCL-X_L inhibitor.

A small molecule that protects macrophages from lethal toxin–induced pyroptosis reveals a kinase-independent role for protein kinase R in caspase-1 activation.