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| | ==Crystal structure of MINDY-1 tMIU in complex with K48-diUb== | | ==Crystal structure of MINDY-1 tMIU in complex with K48-diUb== |
| - | <StructureSection load='5mn9' size='340' side='right' caption='[[5mn9]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='5mn9' size='340' side='right'caption='[[5mn9]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mn9]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MN9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MN9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mn9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MN9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MN9 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FAM63A, KIAA1390 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.05Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=5mn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mn9 OCA], [https://pdbe.org/5mn9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mn9 RCSB], [https://www.ebi.ac.uk/pdbsum/5mn9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mn9 ProSAT]</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=5mn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mn9 OCA], [http://pdbe.org/5mn9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mn9 RCSB], [http://www.ebi.ac.uk/pdbsum/5mn9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mn9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RS27A_BOVIN RS27A_BOVIN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome. | + | [https://www.uniprot.org/uniprot/RS27A_BOVIN RS27A_BOVIN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ubiquitinyl hydrolase 1]] | + | [[Category: Large Structures]] |
| - | [[Category: Kristariyanto, Y A]]
| + | [[Category: Abdul Rehman SA]] |
| - | [[Category: Kulathu, Y]]
| + | [[Category: Kristariyanto YA]] |
| - | [[Category: Rehman, S A.Abdul]] | + | [[Category: Kulathu Y]] |
| - | [[Category: Hydrolase]] | + | |
| - | [[Category: Hydrolase and cysteine protease]] | + | |
| - | [[Category: Motif interacting with ubiquitin]]
| + | |
| - | [[Category: Ubiquitin binding domain]]
| + | |
| Structural highlights
Function
RS27A_BOVIN Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome.
Publication Abstract from PubMed
The eight different types of ubiquitin (Ub) chains that can be formed play important roles in diverse cellular processes. Linkage-selective recognition of Ub chains by Ub-binding domain (UBD)-containing proteins is central to coupling different Ub signals to specific cellular responses. The motif interacting with ubiquitin (MIU) is a small UBD that has been characterized for its binding to monoUb. The recently discovered deubiquitinase MINDY-1/FAM63A contains a tandem MIU repeat (tMIU) that is highly selective at binding to K48-linked polyUb. We here identify that this linkage-selective binding is mediated by a single MIU motif (MIU2) in MINDY-1. The crystal structure of MIU2 in complex with K48-linked polyubiquitin chains reveals that MIU2 on its own binds to all three Ub moieties in an open conformation that can only be accommodated by K48-linked triUb. The weak Ub binder MIU1 increases overall affinity of the tMIU for polyUb chains without affecting its linkage selectivity. Our analyses reveal new concepts for linkage selectivity and polyUb recognition by UBDs.
A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains.,Kristariyanto YA, Abdul Rehman SA, Weidlich S, Knebel A, Kulathu Y EMBO Rep. 2017 Jan 12. pii: e201643205. doi: 10.15252/embr.201643205. PMID:28082312[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kristariyanto YA, Abdul Rehman SA, Weidlich S, Knebel A, Kulathu Y. A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains. EMBO Rep. 2017 Jan 12. pii: e201643205. doi: 10.15252/embr.201643205. PMID:28082312 doi:http://dx.doi.org/10.15252/embr.201643205
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