September 2008 Archives

In the September 19, 2008 issue of Cell, we report striking conformational rearrangements in the crystal structure of NEDD8~Cul5ctd-Rbx1 and SAXS analysis of NEDD8~Cul1ctd-Rbx1 relative to their unmodified counterparts. These results point to conformational control of Cullin-RING ligase (CRL) activity, with ligation of NEDD8 shifting equilibria to disfavor inactive closed architectures, and favor dynamic, open forms that promote polyubiquitination.

Cullin-RING ligases (CRLs) comprise the largest ubiquitin E3 subclass, in which a central cullin subunit links a substrate-binding adaptor with an E2-binding RING. Covalent attachment of the ubiquitin-like protein NEDD8 to a conserved C-terminal domain (ctd) lysine stimulates CRL ubiquitination activity and prevents binding of the inhibitor CAND1. Here we report striking conformational rearrangements in the crystal structure of NEDD8~Cul5ctd-Rbx1 and SAXS analysis of NEDD8~Cul1ctd-Rbx1 relative to their unmodified counterparts. In NEDD8ylated CRL structures, the cullin WHB and Rbx1 RING subdomains are dramatically reoriented, eliminating a CAND1-binding site and imparting multiple potential catalytic geometries to an associated E2. Biochemical analyses indicate that the structural malleability is important for both CRL NEDD8ylation and subsequent ubiquitination activities. Thus, our results point to a conformational control of CRL activity, with ligation of NEDD8 shifting equilibria to disfavor inactive CAND1-bound closed architectures, and favor dynamic, open forms that promote polyubiquitination.

figC1.gif

6 Week Autumn Shutdown

|

Due to DOE budget cuts and planned upgrades to the ALS storage ring we will have no light until October 11th.

Hopefully we will be scheduling beamtime for Oct/Nov/Dec within the next couple of weeks. If you are interested in obtaining General Users shifts please fill out an online application.

ALS Ring Status

loading ...
als current sparkline

Funding

Archives

Powered by Movable Type 5.2.13

March 2017

Sun Mon Tue Wed Thu Fri Sat
      1 2 3 4
5 6 7 8 9 10 11
12 13 14 15 16 17 18
19 20 21 22 23 24 25
26 27 28 29 30 31  
‚Äč