PDBsum entry 2bwe

Signaling protein

PDB id: 2bwe

Contents

Protein chains

(+ 0 more) 46 a.a. *

48 a.a. *

(+ 3 more) 48 a.a. *

73 a.a. *

Waters ×101

* Residue conservation analysis

PDB id:

2bwe

Name:

Signaling protein

Title:

The crystal structure of the complex between the uba and ubl domains of dsk2

Structure:

Dsk2. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p, q, r. Fragment: uba domain, residues 324-327. Engineered: yes. Other_details: uba domain of dsk2, residues 326-373 of the intact protein. Dsk2. Chain: s, t, u. Fragment: ubl domain, residues 1-75.

Source:

Saccharomyces cerevisiae. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Pentamer (from PQS)

Resolution:

3.10Å R-factor: 0.241 R-free: 0.267

Authors:

E.D.Lowe,N.Hasan,J.-F.Trempe,L.Fonso,M.E.M.Noble,J.A.Endicott, L.N.Johnson,N.R.Brown

Key ref:

E.D.Lowe et al. (2006). Structures of the Dsk2 UBL and UBA domains and their complex. Acta Crystallogr D Biol Crystallogr, 62, 177-188. PubMed id: 16421449 DOI: 10.1107/S0907444905037777

Date:

13-Jul-05 Release date: 25-Jan-06

Protein chains

P48510  (DSK2_YEAST) -  Ubiquitin domain-containing protein DSK2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 373 a.a.

Struc: 46 a.a.*

Protein chains

P48510  (DSK2_YEAST) -  Ubiquitin domain-containing protein DSK2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 373 a.a.

Struc: 48 a.a.*

Protein chains

P48510  (DSK2_YEAST) -  Ubiquitin domain-containing protein DSK2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 373 a.a.

Struc: 48 a.a.*

Protein chains

P48510  (DSK2_YEAST) -  Ubiquitin domain-containing protein DSK2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 373 a.a.

Struc: 73 a.a.

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

DOI no: 10.1107/S0907444905037777

Acta Crystallogr D Biol Crystallogr 62:177-188 (2006)

PubMed id: 16421449

Structures of the Dsk2 UBL and UBA domains and their complex.

E.D.Lowe, N.Hasan, J.F.Trempe, L.Fonso, M.E.Noble, J.A.Endicott, L.N.Johnson, N.R.Brown.

ABSTRACT

The yeast proteins Dsk2 and Rad23 belong to a family of proteins that contain an N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated domain (UBA). Both Dsk2 and Rad23 function as adaptors to target ubiquitin-labelled proteins to the proteasome through recognition of polyubiquitin (four or more K48-linked ubiquitins) by their UBA domains and to the yeast proteasomal subunit Rpn1 by their UBL domains. The crystal structures of the Dsk2 UBL domain, the Dsk2 UBA domain and the Dsk2 UBA-UBL complex are reported. In the crystal, the Dsk2 UBA domains associate through electrostatic interactions to form ninefold helical ribbons that leave the ubiquitin-binding surface exposed. The UBA-UBL complex explains the reduced affinity of the UBA domain for UBL compared with ubiquitin and has implications for the regulation of Dsk2 adaptor function during ubiquitin-mediated proteasomal targeting. A model is discussed in which two or more Dsk2 UBA molecules may selectively bind to K48-linked polyubiquitin.

Selected figure(s)

Figure 5.
Contacts at the UBA-UBL interface. (a) Schematic representation of UBL (cyan) and UBA (green) showing the contact regions between UBA residues from the end of [alpha] 1 helix, the [alpha] 1/ [alpha] 2 loop and the [alpha] 3 helix with residues from UBL from the [beta] 3, [beta] 4 and [beta] 5 strands. (b) Details of the contacts using the same colouring scheme as in (a). All residues from UBA and UBL that make contacts of <4.5 Å are shown. These are UBA residues D341, M342, G343, F344, Q362, L365, D366, L369 and G371 and UBL residues R43, I45, S47, G48, I50, H69, V71 and K72. The view is rotated ~ 90° about the vertical axis from (a). (c) The van der Waals surface of UBL as seen by the UBA molecule with the UBA molecule and interacting residues superimposed. The hydrophobic potential (Goodford, 1985 [Goodford, P. J. (1985). J. Med. Chem. 28, 849-858.]-[bluearr.gif] ) of the surface is coloured with the deepest hydrophobicity yellow, the middle range in magenta and the surface with neutral hydrophobic potential in grey (J. Gruber & M. E. M. Noble, unpublished work). The surface has been made partially transparent to reveal the UBL structure and interacting residues. The UBL structure without the surface is shown on the right. The view is similar to (b) and 90° from (a). (d) A view 180° from (c) showing the van der Waals surface of UBA as seen by the UBL molecule, with the UBL molecule and interacting residues superimposed. The colouring is as in (c). The UBA molecule without the surface is shown on the right.

Figure 6.
(a) Comparison of the Dsk2 UBA-UBL complex (green and cyan, respectively) with the Dsk2 UBA-Ub complex (magenta and orange, respectively; from Ohno et al., 2005 [Ohno, A., Jee, J., Fujiwara, K., Tenno, T., Goda, N., Tochio, H., Kobayashi, H., Horoaki, H. & Shirakawa, M. (2005). Structure, 13, 521-532.]-[bluearr.gif] ). The major differences at the interface are at the [beta] 1/ [beta] 2 loop and the [beta] 3/ [beta] 4 loop of UBL and Ub. Further details are described in the text. (b) A simplified view of the contacts between Ub (gold) and UBA (magenta) (left) and UBL (cyan) and UBA (green) (right) showing the domains in the same orientation as Fig. 6 [link]-[turqarr.gif] (a). Only the most significant contacts that differ between the two structures are shown. The Ub-UBA interface has contacts from Ub residues K6 and L8 to UBA residues which are not made in the UBBL-UBA complex. The UBL-UBA complex has closer contacts between I45 and I50 with UBA residues L365 and L369 that in the Ub-UBA complex. Full details of the contacts are given in the supplementary material.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 177-188) copyright 2006.

Figures were selected by the author.