Y-Family Polymerase Conformation Is a Major Determinant of Fidelity and Translesion Specificity

1. Download : Download high-res image (246KB)
2. Download : Download full-size image

Highlights? Y-family polymerases differ in fidelity and translesion synthesis specificity ? Polymerase fidelity and specificity are controlled by the interdomain linker ? Three amino acids in the interdomain linker are sufficient to determine conformation ? Differences in polymerase conformation determine differences in polymerase activity     

Identification of the Outer-Inner Dynein Linker as a Hub Controller for Axonemal Dynein Activities

1. Download : Download high-res image (280KB)
2. Download : Download full-size image

Highlights? Outer dynein intermediate chain 2 (IC2) forms the outer-inner dynein (OID) linker ? A mutation to IC2 nonspecifically activates the outer dynein activity ? The mutation to IC2 alters the inner-dynein-dependent flagellar waveform ? The OID linker regulates flagellar beating by controlling outer and inner dyneins     

An efficient null model for conformational fluctuations in proteins

1. Download : Download high-res image (211KB)
2. Download : Download full-size image

Highlights? TYPHON explores a protein's conformational space under given nonlocal restraints ? TYPHON's advanced probabilistic models ensure protein-like local structure ? TYPHON can reproduce a range of experimental results ? TYPHON's computational efficiency makes large scale screening efforts possible     

Intrinsic negative feedback governs activation surge in two-component regulatory systems

1. Download : Download high-res image (175KB)
2. Download : Download full-size image

Highlights? Activation surge reconstituted in vitro with purified SK and RR ? ADP can be endogenously generated from ATP to stimulate an SK's phosphatase activity ? SK's affinity for ADP governs the switch from the kinase to phosphatase state ? Lid region of SK PhoQ controls its phosphatase activity and surge of RR PhoP     

Supertertiary Structure of the MAGUK Core from PSD-95

1. Download : Download high-res image (177KB)
2. Download : Download full-size image

Highlights? Using NMR and SAXS, we depict the dynamic structure of the MAGUK core PSD-95 ? PDZ3 of the MAGUK core interacts with SH3 via its canonical peptide binding groove ? Binding of PDZ peptides, such as CRIPT, disrupts the interaction between PDZ3 and SH3 ? Rosetta modeling shows that linker residues L411/M412 dock into the PDZ3 binding site     

Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen

1. Download : Download full-size image

Highlights? Cocrystal structure reveals multidomain SV40 large T binding to DNA ? Dimeric LTag bound to origin DNA is intermediate in initiator-helicase assembly ? Interplay among OBD, Zn, and AAA+ domains enables recognition of origin DNA ? DNA shape readout can be mediated through histidine contacts with the minor groove     

PGC-1 Coactivators Regulate MITF and the Tanning Response

1. Download : Download high-res image (175KB)
2. Download : Download full-size image

Highlights? PGC-1 induces pigment formation in melanocytes ? PGC-1s activate expression of MITF ? α-MSH induces PGC-1s, which are required for induction of melanogenic genes ? eQTLs in human PGC-1β are associated with tanning ability and melanoma protection     

A dysregulated endocannabinoid-eicosanoid network supports pathogenesis in a mouse model of Alzheimer's disease

1. Download : Download full-size image

Highlights? Monoacylglycerol lipase (MAGL) is a major contributor to brain arachidonic acid pools ? MAGL mutation decreases neuroinflammation and amyloid β in Alzheimer's disease mouse ? MAGL blockade recapitulates brain prostaglandin and cytokine-lowering effects ? MAGL inhibitors may be a next-generation strategy for combating Alzheimer's disease     

RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor

1. Download : Download high-res image (257KB)
2. Download : Download full-size image

Highlights? Crystal structures of the cytokine-binding regions of OPG and RANK bound to RANKL ? High-affinity OPG engagement is associated with a distinct RANKL-binding cleft ? Structural basis of how the OPG^F96L mutation promotes juvenile Paget’s disease     

Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration

1. Download : Download high-res image (85KB)
2. Download : Download full-size image

Highlights? Cardiac injury induces structural and molecular changes in zebrafish endocardium ? Endocardial and epicardial cells at the site of injury synthesize retinoic acid (RA) ? The extent of this injury response correlates with a species' regenerative capacity ? Regenerative cardiomyocyte proliferation in zebrafish requires retinoic acid signaling     

Phage pierces the host cell membrane with the iron-loaded spike

1. Download : Download high-res image (389KB)
2. Download : Download full-size image

Highlights? Phage tails and other contractile injection systems contain a central spike protein ? The tip of the spike is “hardened” by a centrally positioned iron ion ? The spike appears to pierce the host cell membrane without unfolding ? An OB-fold with an extra β-hairpin is a conserved feature of all central spikes     

Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA

1. Download : Download high-res image (422KB)
2. Download : Download full-size image

Highlights? Neil3 is an Fpg/Nei DNA glycosylase of the base excision repair pathway ? Neil3 excises a broad spectrum of base lesions, with a marked preference for ssDNA ? We report a crystal structure of Neil3 DNA glycosylase ? The structure provides valuable insights into Neil3′s unusual substrate specificity     

Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity

1. Download : Download high-res image (241KB)
2. Download : Download full-size image

Highlights? EM structure of the CMR complex for viral RNA degradation has been determined ? The crRNA content of CMR has been analyzed by deep sequencing ? Target RNA cleavage by CMR is sequence dependent     

Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aβ and Differential Drug Responsiveness

1. Download : Download high-res image (241KB)
2. Download : Download full-size image

Highlights? Familial and sporadic Alzheimer’s patient iPSC-derived neural cells were analyzed ? Intracellular Aβ oligomers accumulate in lines from some patients ? Aβ oligomer accumulation is associated with ER and oxidative stress ? DHA-alleviated ER and oxidative stresses improve cell viability     

Structure of the Pentameric Ligand-Gated Ion Channel GLIC Bound with Anesthetic Ketamine

1. Download : Download high-res image (335KB)
2. Download : Download full-size image

Highlights? The structure of ketamine-bound GLIC reveals an anesthetic binding site ? The study provides compelling evidence for allosteric inhibition by anesthetics ? Ketamine inhibition on GLIC is similar to competitive antagonist action on nAChRs ? Ketamine directly acts on pLGICs in addition to NMDA receptors     

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

1. Download : Download high-res image (167KB)
2. Download : Download full-size image

Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

A Predictive Computational Model of the Dynamic 3D Interphase Yeast Nucleus

1. Download : Download high-res image (367KB)
2. Download : Download full-size image

Highlights? We describe a predictive computational model of dynamic chromosomes in the yeast nucleus ? The model quantitatively recapitulates experimental data on nuclear organization ? The model predicts nuclear reorganization in response to treatment by rapamycin ? Large-scale nuclear organization is dominated by unspecific effects of crowded polymers     

Dopamine controls neurogenesis in the adult salamander midbrain in homeostasis and during regeneration of dopamine neurons

1. Download : Download high-res image (422KB)
2. Download : Download full-size image

Highlights? Regeneration of midbrain dopamine neurons depends on decreased dopamine signaling ? L-dopa inhibits ependymoglia cell proliferation during dopamine neuron regeneration ? Proliferation of ependymoglia cells is constantly suppressed by dopamine signaling ? Inhibition of dopamine signaling evokes neurogenesis by quiescent ependymoglia cells     

The Centrosome Regulates the Rab11- Dependent Recycling Endosome Pathway at Appendages of the Mother Centriole

1. Download : Download high-res image (153KB)
2. Download : Download full-size image

Highlights? Endosome-proteins localize to centrosomes independent of membranes ? Rab11 and its modulators localize to mother centriole appendages ? Mother centriole appendages regulate membrane recycling through Rab11