2nvu
From Proteopedia
(New page: 200px<br /> <applet load="2nvu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2nvu, resolution 2.80Å" /> '''Structure of APPBP1...) |
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| - | [[Image:2nvu.gif|left|200px]]<br /> | + | [[Image:2nvu.gif|left|200px]]<br /><applet load="2nvu" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2nvu" size=" | + | |
caption="2nvu, resolution 2.80Å" /> | caption="2nvu, resolution 2.80Å" /> | ||
'''Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex'''<br /> | '''Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme | + | Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme cascades. E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, forming a covalent E1 throught UBL thioester intermediate, and generating a thioester-linked E2 throught UBL product, which must be released for subsequent reactions. Here we report the structural analysis of a trapped UBL activation complex for the human NEDD8 pathway, containing NEDD8's heterodimeric E1 (APPBP1-UBA3), two NEDD8s (one thioester-linked to E1, one noncovalently associated for adenylation), a catalytically inactive E2 (Ubc12), and MgATP. The results suggest that a thioester switch toggles E1-E2 affinities. Two E2 binding sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking E1 conformational change. The other comes directly from the thioester-bound NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation would facilitate release of the E2 throught NEDD8 thioester product. Thus, transferring the UBL's thioester linkage between successive conjugation enzymes can induce conformational changes and alter interaction networks to drive consecutive steps in UBL cascades. |
==About this Structure== | ==About this Structure== | ||
| - | 2NVU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, ZN and ATP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2NVU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NVU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Holton, J | + | [[Category: Holton, J M.]] |
| - | [[Category: Huang, D | + | [[Category: Huang, D T.]] |
| - | [[Category: Hunt, H | + | [[Category: Hunt, H W.]] |
| - | [[Category: Ohi, M | + | [[Category: Ohi, M D.]] |
| - | [[Category: Schulman, B | + | [[Category: Schulman, B A.]] |
[[Category: Zhuang, M.]] | [[Category: Zhuang, M.]] | ||
[[Category: ATP]] | [[Category: ATP]] | ||
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[[Category: ubiquitin]] | [[Category: ubiquitin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:11:34 2008'' |
Revision as of 16:11, 21 February 2008
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Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex
Overview
Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme cascades. E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, forming a covalent E1 throught UBL thioester intermediate, and generating a thioester-linked E2 throught UBL product, which must be released for subsequent reactions. Here we report the structural analysis of a trapped UBL activation complex for the human NEDD8 pathway, containing NEDD8's heterodimeric E1 (APPBP1-UBA3), two NEDD8s (one thioester-linked to E1, one noncovalently associated for adenylation), a catalytically inactive E2 (Ubc12), and MgATP. The results suggest that a thioester switch toggles E1-E2 affinities. Two E2 binding sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking E1 conformational change. The other comes directly from the thioester-bound NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation would facilitate release of the E2 throught NEDD8 thioester product. Thus, transferring the UBL's thioester linkage between successive conjugation enzymes can induce conformational changes and alter interaction networks to drive consecutive steps in UBL cascades.
About this Structure
2NVU is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity., Huang DT, Hunt HW, Zhuang M, Ohi MD, Holton JM, Schulman BA, Nature. 2007 Jan 25;445(7126):394-8. Epub 2007 Jan 14. PMID:17220875
Page seeded by OCA on Thu Feb 21 18:11:34 2008
Categories: Homo sapiens | Protein complex | Holton, J M. | Huang, D T. | Hunt, H W. | Ohi, M D. | Schulman, B A. | Zhuang, M. | ATP | MG | ZN | Adenylation | Atp | Conformational change | E1 | E2 | Multifunction macromolecular complex | Nedd8 | Switch | Thioester | Ubiquitin
