Structure of the Cand1-Cul1-Roc1 Complex Reveals Regulatory Mechanisms for the Assembly of the Multisubunit Cullin-Dependent Ubiquitin Ligases

AbstractThe SCF ubiquitin ligase complex regulates diverse cellular functions by ubiquitinating numerous protein substrates. Cand1, a 120 kDa HEAT repeat protein, forms a tight complex with the Cul1-Roc1 SCF catalytic core, inhibiting the assembly of the multisubunit E3 complex. The crystal structure of the Cand1-Cul1-Roc1 complex shows that Cand1 adopts a highly sinuous superhelical structure, clamping around the elongated SCF scaffold protein Cul1. At one end, a Cand1 β hairpin protrusion partially occupies the adaptor binding site on Cul1, inhibiting its interactions with the Skp1 adaptor and the substrate-recruiting F box protein subunits. At the other end, two Cand1 HEAT repeats pack against a conserved Cul1 surface cleft and bury a Cul1 lysine residue, whose modification by the ubiquitin-like protein, Nedd8, is able to block Cand1-Cul1 association. Together with biochemical evidence, these structural results elucidate the mechanisms by which Cand1 and Nedd8 regulate the assembly-disassembly cycles of SCF and other cullin-dependent E3 complexes

Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell 124:105–117

SUMMARY The DDB1-Cul4A ubiquitin ligase complex promotes protein ubiquitination in diverse cellular functions and is reprogrammed by the V proteins of paramyxoviruses to degrade STATs and block interferon signaling. Here we report the crystal structures of DDB1 alone and in complex with the simian virus 5 V protein. The DDB1 structure reveals an intertwined three-propeller cluster, which contains two tightly coupled b propellers with a large pocket in between and a third b propeller flexibly attached on the side. The rigid double-propeller fold of DDB1 is targeted by the viral V protein, which inserts an entire helix into the doublepropeller pocket, whereas the third propeller domain docks DDB1 to the N terminus of the Cul4A scaffold. Together, these results not only provide structural insights into how the virus hijacks the DDB1-Cul4A ubiquitin ligase but also establish a structural framework for understanding the multiple functions of DDB1 in the uniquely assembled cullin-RING E3 machinery

The hadronic final state in e+e−e^{+}e^{-} annihilation at c.m. energies of 13, 17 and 27.4 GeV

Results on the hadronic final state in e/sup +/e/sup -/ annihilation at 13, 17 and 27.4 GeV are presented. There is no compelling evidence for the existence of the t quark in these data, which are in general agreement with a simple quark parton model. Some tentative indications of QCD effects are observed in the p/sub T//sup 2/ distributions

PRODUCTION AND PROPERTIES OF THE tau LEPTON IN e+ e- ANNIHILATION AT c.m. ENERGIES FROM 12-GeV TO 31.6-GeV

We have observed τ production in e+e− annihilation at centre-of-mass energies between 12 and 31.6 GeV with cross sections in agreement with the QED τ-pair cross section. Branching ratios for τ decay have been measured and are consistent with the world averages. We have determined the cutoff parameters of QED Λ+ (Λ−) to be > 73 GeV (82 GeV) and have obtained an upper limit on the τ lifetime of 1.4 × 10−12 s(95% CL)