2p63: Difference between revisions

Revision as of 06:51, 22 August 2018

Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination

Structural highlights

2p63 is a 4 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	MSE
Gene:	CDC4 (ATCC 18824)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CDC4_YEAST] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds to phosphorylated target proteins. Directs ubiquitination of the phosphorylated CDK inhibitor SIC1. Involved in the degradation of CDC6 together with CDC34/UBC3 and CDC53, and in restricting the degradation of FAR1 to the nucleus. Is essential for initiation of DNA replication and separation of the spindle pole bodies to form the poles of the mitotic spindle. It also plays a role in bud development, fusion of zygotic nuclei after conjugation and various aspects of sporulation. Required for HTA1-HTB1 locus transcription activation. Required for G1/S and G2/M transition.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Publication Abstract from PubMed

SCF ubiquitin ligases recruit substrates for degradation via F box protein adaptor subunits. WD40 repeat F box proteins, such as Cdc4 and beta-TrCP, contain a conserved dimerization motif called the D domain. Here, we report that the D domain protomers of yeast Cdc4 and human beta-TrCP form a superhelical homotypic dimer. Disruption of the D domain compromises the activity of yeast SCF(Cdc4) toward the CDK inhibitor Sic1 and other substrates. SCF(Cdc4) dimerization has little effect on the affinity for Sic1 but markedly stimulates ubiquitin conjugation. A model of the dimeric holo-SCF(Cdc4) complex based on small-angle X-ray scatter measurements reveals a suprafacial configuration, in which substrate-binding sites and E2 catalytic sites lie in the same plane with a separation of 64 A within and 102 A between each SCF monomer. This spatial variability may accommodate diverse acceptor lysine geometries in both substrates and the elongating ubiquitin chain and thereby increase catalytic efficiency.

Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination.,Tang X, Orlicky S, Lin Z, Willems A, Neculai D, Ceccarelli D, Mercurio F, Shilton BH, Sicheri F, Tyers M Cell. 2007 Jun 15;129(6):1165-76. PMID:17574027^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kornitzer D, Raboy B, Kulka RG, Fink GR. Regulated degradation of the transcription factor Gcn4. EMBO J. 1994 Dec 15;13(24):6021-30. PMID:7813440
↑ Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 1997 Oct 17;91(2):209-19. PMID:9346238
↑ Feldman RM, Correll CC, Kaplan KB, Deshaies RJ. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell. 1997 Oct 17;91(2):221-30. PMID:9346239
↑ Li FN, Johnston M. Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle. EMBO J. 1997 Sep 15;16(18):5629-38. PMID:9312022 doi:10.1093/emboj/16.18.5629
↑ Drury LS, Perkins G, Diffley JF. The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. EMBO J. 1997 Oct 1;16(19):5966-76. PMID:9312054 doi:10.1093/emboj/16.19.5966
↑ Jaquenoud M, Gulli MP, Peter K, Peter M. The Cdc42p effector Gic2p is targeted for ubiquitin-dependent degradation by the SCFGrr1 complex. EMBO J. 1998 Sep 15;17(18):5360-73. PMID:9736614 doi:10.1093/emboj/17.18.5360
↑ Goh PY, Surana U. Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Aug;19(8):5512-22. PMID:10409741
↑ Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW. Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science. 1999 Apr 23;284(5414):662-5. PMID:10213692
↑ Blondel M, Galan JM, Chi Y, Lafourcade C, Longaretti C, Deshaies RJ, Peter M. Nuclear-specific degradation of Far1 is controlled by the localization of the F-box protein Cdc4. EMBO J. 2000 Nov 15;19(22):6085-97. PMID:11080155 doi:10.1093/emboj/19.22.6085
↑ Tang X, Orlicky S, Lin Z, Willems A, Neculai D, Ceccarelli D, Mercurio F, Shilton BH, Sicheri F, Tyers M. Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination. Cell. 2007 Jun 15;129(6):1165-76. PMID:17574027 doi:10.1016/j.cell.2007.04.042

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Kornitzer D, Raboy B, Kulka RG, Fink GR. Regulated degradation of the transcription factor Gcn4. EMBO J. 1994 Dec 15;13(24):6021-30. PMID:7813440

[2] Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 1997 Oct 17;91(2):209-19. PMID:9346238

[3] Feldman RM, Correll CC, Kaplan KB, Deshaies RJ. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell. 1997 Oct 17;91(2):221-30. PMID:9346239

[4] Li FN, Johnston M. Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle. EMBO J. 1997 Sep 15;16(18):5629-38. PMID:9312022 doi:10.1093/emboj/16.18.5629

[5] Drury LS, Perkins G, Diffley JF. The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. EMBO J. 1997 Oct 1;16(19):5966-76. PMID:9312054 doi:10.1093/emboj/16.19.5966

[6] Jaquenoud M, Gulli MP, Peter K, Peter M. The Cdc42p effector Gic2p is targeted for ubiquitin-dependent degradation by the SCFGrr1 complex. EMBO J. 1998 Sep 15;17(18):5360-73. PMID:9736614 doi:10.1093/emboj/17.18.5360

[7] Goh PY, Surana U. Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Aug;19(8):5512-22. PMID:10409741

[8] Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW. Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science. 1999 Apr 23;284(5414):662-5. PMID:10213692

[9] Blondel M, Galan JM, Chi Y, Lafourcade C, Longaretti C, Deshaies RJ, Peter M. Nuclear-specific degradation of Far1 is controlled by the localization of the F-box protein Cdc4. EMBO J. 2000 Nov 15;19(22):6085-97. PMID:11080155 doi:10.1093/emboj/19.22.6085

[10] Tang X, Orlicky S, Lin Z, Willems A, Neculai D, Ceccarelli D, Mercurio F, Shilton BH, Sicheri F, Tyers M. Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination. Cell. 2007 Jun 15;129(6):1165-76. PMID:17574027 doi:10.1016/j.cell.2007.04.042

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@@ Line 1: / Line 1: @@
 ==Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination==
 <StructureSection load='2p63' size='340' side='right' caption='[[2p63]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDC4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p63 OCA], [http://pdbe.org/2p63 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p63 RCSB], [http://www.ebi.ac.uk/pdbsum/2p63 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p63 OCA], [http://pdbe.org/2p63 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p63 RCSB], [http://www.ebi.ac.uk/pdbsum/2p63 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p63 ProSAT]</span></td></tr>
 </table>
 == Function ==

2p63: Difference between revisions

Revision as of 06:51, 22 August 2018

Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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