5ucl

From Proteopedia

(Difference between revisions)

Revision as of 16:14, 22 March 2017

Ubiquitin Variant in Complex with Binding Partner

Structural highlights

5ucl is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[VPS27_YEAST] Component of the ESCRT-0 complex which is the sorting receptor for ubiquitinated cargo proteins at the multivesicular body (MVB) and recruits ESCRT-I to the MVB outer membrane. Controls exit from the prevacuolar compartment (PVC) in both the forward direction to the vacuole and the return to the Golgi. Allows VPS10 to return to the (trans-Golgi network) TGN from the PVC. Might also function as an alternate adapter in the COPIb clathrin-like coat.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16]

Publication Abstract from PubMed

Ubiquitin interacting motifs (UIMs) are short alpha-helices found in a number of eukaryotic proteins. UIMs interact weakly but specifically with ubiquitin conjugated to other proteins, and in so doing, mediate specific cellular signals. Here we used phage display to generate ubiquitin variants (UbVs) targeting the N-terminal UIM of the yeast Vps27 protein. Selections yielded UbV.v27.1, which recognized the cognate UIM with high specificity relative to other yeast UIMs and bound with an affinity more than two orders of magnitude higher than that of ubiquitin. Structural and mutational studies of the UbV.v27.1-UIM complex revealed the molecular details for the enhanced affinity and specificity of UbV.v27.1, and underscored the importance of changes at the binding interface as well as at positions that do not contact the UIM. Our study highlights the power of the phage display approach for selecting UbVs with unprecedented affinity and high selectivity for particular alpha-helical UIM domains within proteomes, and it establishes a general approach for the development of inhibitors targeting interactions of this type. This article is protected by copyright. All rights reserved.

Structural and functional characterization of a ubiquitin variant engineered for tight and specific binding to an alpha-helical ubiquitin interacting motif.,Manczyk N, Yates BP, Veggiani G, Ernst A, Sicheri F, Sidhu SS Protein Sci. 2017 Mar 9. doi: 10.1002/pro.3155. PMID:28276594^[17]

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

References

↑ Robinson JS, Klionsky DJ, Banta LM, Emr SD. Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol Cell Biol. 1988 Nov;8(11):4936-48. PMID:3062374
↑ Raymond CK, Howald-Stevenson I, Vater CA, Stevens TH. Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants. Mol Biol Cell. 1992 Dec;3(12):1389-402. PMID:1493335
↑ Nothwehr SF, Bryant NJ, Stevens TH. The newly identified yeast GRD genes are required for retention of late-Golgi membrane proteins. Mol Cell Biol. 1996 Jun;16(6):2700-7. PMID:8649377
↑ Bryant NJ, Stevens TH. Two separate signals act independently to localize a yeast late Golgi membrane protein through a combination of retrieval and retention. J Cell Biol. 1997 Jan 27;136(2):287-97. PMID:9015300
↑ Luo W, Chang A. Novel genes involved in endosomal traffic in yeast revealed by suppression of a targeting-defective plasma membrane ATPase mutant. J Cell Biol. 1997 Aug 25;138(4):731-46. PMID:9265642
↑ Gerrard SR, Levi BP, Stevens TH. Pep12p is a multifunctional yeast syntaxin that controls entry of biosynthetic, endocytic and retrograde traffic into the prevacuolar compartment. Traffic. 2000 Mar;1(3):259-69. PMID:11208109
↑ Dupre S, Haguenauer-Tsapis R. Deubiquitination step in the endocytic pathway of yeast plasma membrane proteins: crucial role of Doa4p ubiquitin isopeptidase. Mol Cell Biol. 2001 Jul;21(14):4482-94. PMID:11416128 doi:10.1128/MCB.21.14.4482-4494.2001
↑ Bilodeau PS, Urbanowski JL, Winistorfer SC, Piper RC. The Vps27p Hse1p complex binds ubiquitin and mediates endosomal protein sorting. Nat Cell Biol. 2002 Jul;4(7):534-9. PMID:12055639 doi:10.1038/ncb815
↑ Prescianotto-Baschong C, Riezman H. Ordering of compartments in the yeast endocytic pathway. Traffic. 2002 Jan;3(1):37-49. PMID:11872141
↑ Katzmann DJ, Stefan CJ, Babst M, Emr SD. Vps27 recruits ESCRT machinery to endosomes during MVB sorting. J Cell Biol. 2003 Aug 4;162(3):413-23. PMID:12900393 doi:http://dx.doi.org/10.1083/jcb.200302136
↑ Bilodeau PS, Winistorfer SC, Kearney WR, Robertson AD, Piper RC. Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome. J Cell Biol. 2003 Oct 27;163(2):237-43. PMID:14581452 doi:10.1083/jcb.200305007
↑ Eguez L, Chung YS, Kuchibhatla A, Paidhungat M, Garrett S. Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar protein sorting. Genetics. 2004 May;167(1):107-17. PMID:15166140
↑ Eugster A, Pecheur EI, Michel F, Winsor B, Letourneur F, Friant S. Ent5p is required with Ent3p and Vps27p for ubiquitin-dependent protein sorting into the multivesicular body. Mol Biol Cell. 2004 Jul;15(7):3031-41. Epub 2004 Apr 23. PMID:15107463 doi:10.1091/mbc.E03-11-0793
↑ Bowers K, Lottridge J, Helliwell SB, Goldthwaite LM, Luzio JP, Stevens TH. Protein-protein interactions of ESCRT complexes in the yeast Saccharomyces cerevisiae. Traffic. 2004 Mar;5(3):194-210. PMID:15086794 doi:10.1111/j.1600-0854.2004.00169.x
↑ Gabriely G, Kama R, Gerst JE. Involvement of specific COPI subunits in protein sorting from the late endosome to the vacuole in yeast. Mol Cell Biol. 2007 Jan;27(2):526-40. Epub 2006 Nov 13. PMID:17101773 doi:MCB.00577-06
↑ Curtiss M, Jones C, Babst M. Efficient cargo sorting by ESCRT-I and the subsequent release of ESCRT-I from multivesicular bodies requires the subunit Mvb12. Mol Biol Cell. 2007 Feb;18(2):636-45. Epub 2006 Nov 29. PMID:17135292 doi:E06-07-0588
↑ Manczyk N, Yates BP, Veggiani G, Ernst A, Sicheri F, Sidhu SS. Structural and functional characterization of a ubiquitin variant engineered for tight and specific binding to an alpha-helical ubiquitin interacting motif. Protein Sci. 2017 Mar 9. doi: 10.1002/pro.3155. PMID:28276594 doi:http://dx.doi.org/10.1002/pro.3155

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ucl"

Categories: Manczyk, N | Sicheri, F | Protein binding | Ubiquitin variant | Uim

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5ucl is ON HOLD  until Paper Publication
+==Ubiquitin Variant in Complex with Binding Partner==
+<StructureSection load='5ucl' size='340' side='right' caption='[[5ucl]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5ucl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UCL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UCL FirstGlance]. <br>
+</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=5ucl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ucl OCA], [http://pdbe.org/5ucl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ucl RCSB], [http://www.ebi.ac.uk/pdbsum/5ucl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ucl ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/VPS27_YEAST VPS27_YEAST]] Component of the ESCRT-0 complex which is the sorting receptor for ubiquitinated cargo proteins at the multivesicular body (MVB) and recruits ESCRT-I to the MVB outer membrane. Controls exit from the prevacuolar compartment (PVC) in both the forward direction to the vacuole and the return to the Golgi. Allows VPS10 to return to the (trans-Golgi network) TGN from the PVC. Might also function as an alternate adapter in the COPIb clathrin-like coat.<ref>PMID:3062374</ref> <ref>PMID:1493335</ref> <ref>PMID:8649377</ref> <ref>PMID:9015300</ref> <ref>PMID:9265642</ref> <ref>PMID:11208109</ref> <ref>PMID:11416128</ref> <ref>PMID:12055639</ref> <ref>PMID:11872141</ref> <ref>PMID:12900393</ref> <ref>PMID:14581452</ref> <ref>PMID:15166140</ref> <ref>PMID:15107463</ref> <ref>PMID:15086794</ref> <ref>PMID:17101773</ref> <ref>PMID:17135292</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ubiquitin interacting motifs (UIMs) are short alpha-helices found in a number of eukaryotic proteins. UIMs interact weakly but specifically with ubiquitin conjugated to other proteins, and in so doing, mediate specific cellular signals. Here we used phage display to generate ubiquitin variants (UbVs) targeting the N-terminal UIM of the yeast Vps27 protein. Selections yielded UbV.v27.1, which recognized the cognate UIM with high specificity relative to other yeast UIMs and bound with an affinity more than two orders of magnitude higher than that of ubiquitin. Structural and mutational studies of the UbV.v27.1-UIM complex revealed the molecular details for the enhanced affinity and specificity of UbV.v27.1, and underscored the importance of changes at the binding interface as well as at positions that do not contact the UIM. Our study highlights the power of the phage display approach for selecting UbVs with unprecedented affinity and high selectivity for particular alpha-helical UIM domains within proteomes, and it establishes a general approach for the development of inhibitors targeting interactions of this type. This article is protected by copyright. All rights reserved.
-Authors:
+Structural and functional characterization of a ubiquitin variant engineered for tight and specific binding to an alpha-helical ubiquitin interacting motif.,Manczyk N, Yates BP, Veggiani G, Ernst A, Sicheri F, Sidhu SS Protein Sci. 2017 Mar 9. doi: 10.1002/pro.3155. PMID:28276594<ref>PMID:28276594</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5ucl" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Manczyk, N]]
+[[Category: Sicheri, F]]
+[[Category: Protein binding]]
+[[Category: Ubiquitin variant]]
+[[Category: Uim]]

5ucl

From Proteopedia

Revision as of 16:14, 22 March 2017

Ubiquitin Variant in Complex with Binding Partner

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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