PDBsum entry 2o6v

Signaling protein

PDB id: 2o6v

Contents

Protein chains

75 a.a.

76 a.a.

76 a.a.

Ligands

SO4 ×4

MES ×2

Waters ×149

References listed in PDB file

Key reference

Title

Crystal structure and solution nmr studies of lys48-Linked tetraubiquitin at neutral ph.

Authors

M.J.Eddins, R.Varadan, D.Fushman, C.M.Pickart, C.Wolberger.

Ref.

J Mol Biol, 2007, 367, 204-211. [DOI no: 10.1016/j.jmb.2006.12.065]

PubMed id

17240395

Abstract

Ubiquitin modification of proteins is used as a signal in many cellular processes. Lysine side-chains can be modified by a single ubiquitin or by a polyubiquitin chain, which is defined by an isopeptide bond between the C terminus of one ubiquitin and a specific lysine in a neighboring ubiquitin. Polyubiquitin conformations that result from different lysine linkages presumably differentiate their roles and ability to bind specific targets and enzymes. However, conflicting results have been obtained regarding the precise conformation of Lys48-linked tetraubiquitin. We report the crystal structure of Lys48-linked tetraubiquitin at near-neutral pH. The two tetraubiquitin complexes in the asymmetric unit show the complete connectivity of the chain and the molecular details of the interactions. This tetraubiquitin conformation is consistent with our NMR data as well as with previous studies of diubiquitin and tetraubiquitin in solution at neutral pH. The structure provides a basis for understanding Lys48-linked polyubiquitin recognition under physiological conditions.

Figure 1.
Figure 1. A new conformation of Lys48-linked tetraubiquitin. The tetraubiquitin coloring from proximal ubiquitin to distal ubiquitin is: yellow–cyan–green–blue (1–2–3–4). Rotating 45° in either direction about the x-axis from the center structure shows the interface of the two diubiquitin subunits (1–2 on the left, 3–4 on the right). Figure 1. A new conformation of Lys48-linked tetraubiquitin. The tetraubiquitin coloring from proximal ubiquitin to distal ubiquitin is: yellow–cyan–green–blue (1–2–3–4). Rotating 45° in either direction about the x-axis from the center structure shows the interface of the two diubiquitin subunits (1–2 on the left, 3–4 on the right).

Figure 6.
Figure 6. The hydrophobic surface stripes on the Lys48-linked tetraubiquitin surface showing the orientation of all the ubiquitin Leu8 side-chains. The tetraubiquitin coloring is the same as for Figure 1, with the proximal ubiquitin 1 yellow, and the distal ubiquitin 4 being blue. The Leu8 side-chains are shown in red with the numbers corresponding to the specific ubiquitin in the chain a particular Leu8 is from. Figure 6. The hydrophobic surface stripes on the Lys48-linked tetraubiquitin surface showing the orientation of all the ubiquitin Leu8 side-chains. The tetraubiquitin coloring is the same as for [3]Figure 1, with the proximal ubiquitin 1 yellow, and the distal ubiquitin 4 being blue. The Leu8 side-chains are shown in red with the numbers corresponding to the specific ubiquitin in the chain a particular Leu8 is from.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 367, 204-211) copyright 2007.