|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='6o60' size='340' side='right'caption='[[6o60]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='6o60' size='340' side='right'caption='[[6o60]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6o60]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O60 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O60 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6o60]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O60 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.503Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_geranylgeranyltransferase_type_II Protein geranylgeranyltransferase type II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.60 2.5.1.60] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6o60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o60 OCA], [http://pdbe.org/6o60 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o60 RCSB], [http://www.ebi.ac.uk/pdbsum/6o60 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o60 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6o60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o60 OCA], [https://pdbe.org/6o60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o60 RCSB], [https://www.ebi.ac.uk/pdbsum/6o60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o60 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN]] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref> [[http://www.uniprot.org/uniprot/FBXL2_HUMAN FBXL2_HUMAN]] Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin. This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin. Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (PubMed:22020328, PubMed:22323446). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (PubMed:23604317). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (By similarity).[UniProtKB:Q8BH16]<ref>PMID:22020328</ref> <ref>PMID:22323446</ref> <ref>PMID:23604317</ref> [[http://www.uniprot.org/uniprot/PGTB2_HUMAN PGTB2_HUMAN]] Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A. | + | [https://www.uniprot.org/uniprot/PTAR1_HUMAN PTAR1_HUMAN] |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Protein prenylation is believed to be catalyzed by three heterodimeric enzymes: FTase, GGTase1 and GGTase2. Here we report the identification of a previously unknown human prenyltransferase complex consisting of an orphan prenyltransferase alpha-subunit, PTAR1, and the catalytic beta-subunit of GGTase2, RabGGTB. This enzyme, which we named GGTase3, geranylgeranylates FBXL2 to allow its localization at cell membranes, where this ubiquitin ligase mediates the polyubiquitylation of membrane-anchored proteins. In cells, FBXL2 is specifically recognized by GGTase3 despite having a typical carboxy-terminal CaaX prenylation motif that is predicted to be recognized by GGTase1. Our crystal structure analysis of the full-length GGTase3-FBXL2-SKP1 complex reveals an extensive multivalent interface specifically formed between the leucine-rich repeat domain of FBXL2 and PTAR1, which unmasks the structural basis of the substrate-enzyme specificity. By uncovering a missing prenyltransferase and its unique mode of substrate recognition, our findings call for a revision of the 'prenylation code'. |
| | + | |
| | + | GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase.,Kuchay S, Wang H, Marzio A, Jain K, Homer H, Fehrenbacher N, Philips MR, Zheng N, Pagano M Nat Struct Mol Biol. 2019 Jul;26(7):628-636. doi: 10.1038/s41594-019-0249-3. Epub, 2019 Jun 17. PMID:31209342<ref>PMID:31209342</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6o60" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Geranylgeranyl transferase 3D structures|Geranylgeranyl transferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein geranylgeranyltransferase type II]]
| + | [[Category: Wang H]] |
| - | [[Category: Wang, H]] | + | [[Category: Zheng N]] |
| - | [[Category: Zheng, N]] | + | |
| - | [[Category: F-box]]
| + | |
| - | [[Category: Ggtase subunit]]
| + | |
| - | [[Category: Leucine-rich repeat]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PTAR1_HUMAN
Publication Abstract from PubMed
Protein prenylation is believed to be catalyzed by three heterodimeric enzymes: FTase, GGTase1 and GGTase2. Here we report the identification of a previously unknown human prenyltransferase complex consisting of an orphan prenyltransferase alpha-subunit, PTAR1, and the catalytic beta-subunit of GGTase2, RabGGTB. This enzyme, which we named GGTase3, geranylgeranylates FBXL2 to allow its localization at cell membranes, where this ubiquitin ligase mediates the polyubiquitylation of membrane-anchored proteins. In cells, FBXL2 is specifically recognized by GGTase3 despite having a typical carboxy-terminal CaaX prenylation motif that is predicted to be recognized by GGTase1. Our crystal structure analysis of the full-length GGTase3-FBXL2-SKP1 complex reveals an extensive multivalent interface specifically formed between the leucine-rich repeat domain of FBXL2 and PTAR1, which unmasks the structural basis of the substrate-enzyme specificity. By uncovering a missing prenyltransferase and its unique mode of substrate recognition, our findings call for a revision of the 'prenylation code'.
GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase.,Kuchay S, Wang H, Marzio A, Jain K, Homer H, Fehrenbacher N, Philips MR, Zheng N, Pagano M Nat Struct Mol Biol. 2019 Jul;26(7):628-636. doi: 10.1038/s41594-019-0249-3. Epub, 2019 Jun 17. PMID:31209342[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kuchay S, Wang H, Marzio A, Jain K, Homer H, Fehrenbacher N, Philips MR, Zheng N, Pagano M. GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase. Nat Struct Mol Biol. 2019 Jul;26(7):628-636. doi: 10.1038/s41594-019-0249-3. Epub, 2019 Jun 17. PMID:31209342 doi:http://dx.doi.org/10.1038/s41594-019-0249-3
|
