Sandbox Eric Martz

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This article is under collaborative development by Eric Martz (UMass) and Raymond J. Deshaies and his team (CalTech). Please do not edit this page unless you are a member of the development team. Once completed, this page may be moved to a permanent article title.

Proposed article title: Release of RING from Cullin by NEDD8ylation

NEDD8ylation of Cullin-RING

RING (A)   Cullin (C)   NEDD8 (A)

Display chains A/C/R as smoothed backbone traces colored by N->C Rainbow:

N               C

Color traces by chain:

RING (A)   Cullin (C)   NEDD8 (A)

The morph [1] button above shows the transition from a Cullin-RING ligase dimer (3dpl) to the trimer resulting from NEDD8ylation (covalent addition of the NEDD8 ubiquitin-like chain to Lys724 of Cullin; 3dqv). NEDD8 binds and rotates the C-terminal domain of Cullin, releasing the folded RING domain from its Cullin-binding site. RING remains attached to Cullin by the RING N-terminus which remains embedded in Cullin. The contraction and re-expansion of the C-terminal domain during rotation is an artifact of the morphing algorithm.

Cullin atoms within 4.0 Å of:

Colored by Element: C O N

Use the buttons above to show Cullin as a trace in order to see these contacting atoms, then animate the morph. This shows that although the same long alpha helix contacts both RING and NEDD8, the Cullin atoms contacting RING do not, for the most part, contact NEDD8. Important Caveat: The dimer model lacks coordinates for residues 64-66 of RING (green in the N->C Rainbow), which are likely part of the Culllin-RING contact.

Flexibility of Trimer

.

The model 3dqv contains two copies of the trimer in the asymmetric unit. Morphing[2] one to the other shows flexibility of the trimer. The position of RING changes the most because of its flexible tether to Cullin. The two positions of RING in the crystal structure are undoubtedly stabilized by different crystal contacts (not shown here, but could be shown).

To reload the NEDD8ylation morph into Jmol above, simply reload this page.


Notes and References

  1. The 9-model morph file can be downloaded from Image:3dpl 3dqv acr morph.pdb. The morph represents the change from 3dpl to 3dqv, and only chains C and R which are common to these two models. Only one trimer was used from 3dqv (which contains 2 trimers in the asymmetric unit), namely, the one with chains named A, C, and R. This trimer was obtained from PQS as 3dqv_1.mmol. The morph was performed by the Yale Morph Server (beta server), ID b899128-21508. This produced 8 models numbered 0-7. In the product morph, the orientation of the final chains was not changed. Hence, chain A (NEDD8) from 3dqv.pdb was added as model number 8 (9th model) without the need for special alignment. Morph done by Eric Martz at the request of Raymond J. Deshaies of CalTech.
  2. The trimer morph Image:3dqv trimer1 trimer2 morph.pdb.gz was generated from 3dqv_1.mmol and 3dqv_2.mmol (obtained from PQS) with the Yale Morph Server (beta version), ID b318728-3599. The chains B, D, and Y in 3dqv_2.mmol were first renamed to A, C, and R in order to match up with those in 3dqv_1.mmol, using DeepView.
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