A detailed understanding of the molecular mechanisms whereby ubiquitin (Ub) recognizes enzymes in the Ub proteasome system is crucial for understanding the biological function of Ub. Many structures of Ub complexes have been solved and, in most cases, reveal a large structural epitope on a common face of the Ub molecule. However, owing to the generally weak nature of these interactions, it has been difficult to map in detail the functional contributions of individual Ub side chains to affinity and specificity. Here we took advantage of Ub variants (Ubvs) that bind tightly to particular Ub-specific proteases (USPs) and used phage display and saturation scanning mutagenesis to comprehensively map functional epitopes within the structural epitopes. We found that Ubvs that bind to USP2 or USP21 contain a remarkably similar core functional epitope, or "hot spot," consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences. The Ubv core functional epitope contacts residues that are conserved in the human USP family, and thus it is likely important for the interactions of Ub across many family members.
ID: VkahB8tt
Submitter: Marie Ary
Submission Date: June 14, 2017, 5:50 p.m.
Version: 1
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Structure ID | Release Date | Resolution | Structure Title |
---|---|---|---|
5L9U | 2016-06-11T00:00:00+0000 | 6.4 | Model of human Anaphase-promoting complex/Cyclosome (APC/C-CDH1) with a cross linked Ubiquitin variant-substrate-UBE2C (UBCH10) complex representing key features of multiubiquitination |
6ZVK | 2020-07-24T00:00:00+0000 | 3.49 | The Halastavi arva virus (HalV) intergenic region IRES promotes translation by the simplest possible initiation mechanism |
1BT0 | 1998-09-02T00:00:00+0000 | 1.7 | STRUCTURE OF UBIQUITIN-LIKE PROTEIN, RUB1 |
4V8M | 2012-12-09T00:00:00+0000 | 5.57 | High-resolution cryo-electron microscopy structure of the Trypanosoma brucei ribosome |
4V6W | 2013-02-27T00:00:00+0000 | 6.0 | Structure of the D. melanogaster 80S ribosome |
4V6W | 2013-02-27T00:00:00+0000 | 6.0 | Structure of the D. melanogaster 80S ribosome |
5OHM | 2017-07-17T00:00:00+0000 | 3.8 | K33-specific affimer bound to K33 diUb |
4ADX | 2012-01-04T00:00:00+0000 | 6.6 | The Cryo-EM Structure of the Archaeal 50S Ribosomal Subunit in Complex with Initiation Factor 6 |
4V8P | 2011-09-14T00:00:00+0000 | 3.52 | T.thermophila 60S ribosomal subunit in complex with initiation factor 6. |
6NYA | 2019-02-11T00:00:00+0000 | 2.06 | Crystal Structure of ubiquitin E1 (Uba1) in complex with Ubc3 (Cdc34) and ubiquitin |
Percent Identity | Matching Chains | Protein | Accession | Entry Name |
---|---|---|---|---|
97.4 | Ubiquitin variant Ubv.2.1 | P31753 | RS27A_ASPOF | |
100.0 | Ubiquitin variant Ubv.2.1 | P84589 | UBIQ_LUMTE | |
91.4 | Ubiquitin variant Ubv.2.1 | P59272 | RS27A_DAUCA | |
91.7 | Ubiquitin variant Ubv.2.1 | P0C8R3 | RS27B_SCHPO | |
91.7 | Ubiquitin variant Ubv.2.1 | P0C016 | RS27A_SCHPO | |
91.7 | Ubiquitin variant Ubv.2.1 | P27923 | RS27A_MAIZE | |
91.7 | Ubiquitin variant Ubv.2.1 | P47905 | RS27A_LUPAL | |
91.7 | Ubiquitin variant Ubv.2.1 | P0CG87 | RS272_HORVU | |
91.7 | Ubiquitin variant Ubv.2.1 | P0CG86 | RS271_HORVU | |
91.7 | Ubiquitin variant Ubv.2.1 | P59233 | R27AC_ARATH | |
91.7 | Ubiquitin variant Ubv.2.1 | P51431 | R27AB_ORYSJ | |
91.7 | Ubiquitin variant Ubv.2.1 | P59232 | R27AB_ARATH | |
91.7 | Ubiquitin variant Ubv.2.1 | Q9ARZ9 | R27AA_ORYSJ | |
90.8 | Ubiquitin variant Ubv.21.4 | P21899 | RL40_TRYBB | |
90.8 | Ubiquitin variant Ubv.21.4 | Q3E7K8 | UBQ12_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG70 | UBI4P_NEUCR | |
92.0 | Ubiquitin variant Ubv.21.4 | P14799 | RS27A_NEUCR | |
92.1 | Ubiquitin variant Ubv.21.4 | P14795 | RL40_TRYCR | |
92.1 | Ubiquitin variant Ubv.21.4 | P0C224 | RL40_NEUCR | |
92.1 | Ubiquitin variant Ubv.21.4 | P49633 | RL40_ACACA | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH27 | RL402_TRYCR | |
90.8 | Ubiquitin variant Ubv.21.4 | P22589 | UBIQP_PHYIN | |
90.8 | Ubiquitin variant Ubv.21.4 | P42739 | UBIQP_ACEPE | |
90.8 | Ubiquitin variant Ubv.21.4 | P0C032 | RUB3_ORYSJ | |
91.9 | Ubiquitin variant Ubv.2.1 | P14797 | RS27A_DICDI | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH32 | UBQ4_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | Q58G87 | UBQ3_ORYSJ | |
92.1 | Ubiquitin variant Ubv.21.4 | Q1EC66 | UBQ3_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | Q3E7T8 | UBQ14_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH33 | UBQ11_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | Q8H159 | UBQ10_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | P69326 | UBIQ_WHEAT | |
92.1 | Ubiquitin variant Ubv.21.4 | P69317 | UBIQ_LUPPO | |
92.1 | Ubiquitin variant Ubv.21.4 | P69313 | UBIQ_HELAN | |
92.1 | Ubiquitin variant Ubv.21.4 | P69310 | UBIQ_AVESA | |
92.1 | Ubiquitin variant Ubv.21.4 | P69325 | UBIQP_SOYBN | |
92.1 | Ubiquitin variant Ubv.21.4 | P69322 | UBIQP_PEA | |
92.1 | Ubiquitin variant Ubv.21.4 | P69315 | UBIQP_LINUS | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG83 | UBIQP_HORVU | |
92.1 | Ubiquitin variant Ubv.21.4 | P69309 | UBIQP_AVEFA | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CG88 | UBIQJ_DICDI | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CG80 | UBIQI_DICDI | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CG81 | UBIQH_DICDI | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CG79 | UBIQG_DICDI | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CG78 | UBIQF_DICDI | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CG77 | UBIQD_DICDI | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CG76 | UBIQA_DICDI | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG63 | UBI4P_YEAST | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG72 | UBI4P_SCHPO | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG84 | UBI4P_NICSY | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG75 | UBI4P_KLULA | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG74 | UBI4P_CANAX | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH05 | UBI2P_PETCR | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH04 | UBI1P_PETCR | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG85 | UBI1P_NICSY | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CG73 | UBI1P_CANAX | |
92.1 | Ubiquitin variant Ubv.21.4 | P0C031 | RUB2_ORYSJ | |
92.1 | Ubiquitin variant Ubv.21.4 | Q8RUC6 | RUB2_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | P0C030 | RUB1_ORYSJ | |
92.1 | Ubiquitin variant Ubv.21.4 | P0C073 | RUB1_DESAN | |
92.1 | Ubiquitin variant Ubv.21.4 | Q9SHE7 | RUB1_ARATH | |
92.0 | Ubiquitin variant Ubv.21.4 | P05759 | RS31_YEAST | |
92.1 | Ubiquitin variant Ubv.21.4 | P62981 | RS27A_SOLTU | |
92.1 | Ubiquitin variant Ubv.21.4 | P62980 | RS27A_SOLLC | |
92.0 | Ubiquitin variant Ubv.21.4 | P69061 | RS27A_KLULA | |
92.1 | Ubiquitin variant Ubv.21.4 | P49636 | RL40_NICSY | |
93.4 | Ubiquitin variant Ubv.21.4 | P14794 | RL40_DICDI | |
92.1 | Ubiquitin variant Ubv.21.4 | P40909 | RL40_CRYNJ | |
92.1 | Ubiquitin variant Ubv.21.4 | P51423 | RL40_BRARP | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH09 | RL40B_YEAST | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH35 | RL40B_ORYSJ | |
92.1 | Ubiquitin variant Ubv.21.4 | Q42202 | RL40B_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH08 | RL40A_YEAST | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH34 | RL40A_ORYSJ | |
92.1 | Ubiquitin variant Ubv.21.4 | B9DHA6 | RL40A_ARATH | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH07 | RL402_SCHPO | |
92.1 | Ubiquitin variant Ubv.21.4 | P0CH06 | RL401_SCHPO | |
92.1 | Ubiquitin variant Ubv.21.4 | P59271 | R27AA_ARATH | |
93.4 | Ubiquitin variant Ubv.21.4 | P42740 | UBIQP_AGLNE | |
93.4 | Ubiquitin variant Ubv.21.4 | P19848 | UBIQ_COPCO | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CG82 | UBIQP_TETPY | |
93.4 | Ubiquitin variant Ubv.21.4 | P0DJ25 | RL40_TETTS | |
93.4 | Ubiquitin variant Ubv.21.4 | P33190 | RL40_TETPY | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CH10 | RL403_CHLRE | |
93.4 | Ubiquitin variant Ubv.21.4 | P0CH11 | RL401_CHLRE | |
93.2 | Ubiquitin variant Ubv.2.1 | P69200 | RL40_LEITA | |
93.4 | Ubiquitin variant Ubv.21.4 | P69201 | RL40_LEIMA | |
94.7 | Ubiquitin variant Ubv.21.4 | P59669 | UBIQP_GEOCY | |
94.7 | Ubiquitin variant Ubv.21.4 | P0CG71 | UBIQ1_CAEEL | |
94.7 | Ubiquitin variant Ubv.21.4 | P49632 | RL40_CAEEL | |
94.7 | Ubiquitin variant Ubv.21.4 | Q8SWD4 | UBIQ_ENCCU | |
94.7 | Ubiquitin variant Ubv.21.4 | P23398 | UBIQP_STRPU | |
94.7 | Ubiquitin variant Ubv.21.4 | P46575 | RL40_EIMBO | |
96.1 | Ubiquitin variant Ubv.21.4 | P62975 | UBIQ_RABIT | |
96.1 | Ubiquitin variant Ubv.21.4 | P68197 | UBIQ_CERCA | |
96.1 | Ubiquitin variant Ubv.21.4 | Q865C5 | UBIQ_CAMDR | |
96.1 | Ubiquitin variant Ubv.21.4 | P62972 | UBIQP_XENLA | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG69 | UBIQP_DROME | |
96.1 | Ubiquitin variant Ubv.21.4 | P62976 | UBIQP_CRIGR | |
96.1 | Ubiquitin variant Ubv.21.4 | Q63429 | UBC_RAT | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG61 | UBC_PONPY | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG68 | UBC_PIG | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG64 | UBC_PANTR | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG50 | UBC_MOUSE | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG48 | UBC_HUMAN | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG66 | UBC_GORGO | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CH28 | UBC_BOVIN | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG55 | UBB_SHEEP | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG51 | UBB_RAT | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG60 | UBB_PONPY | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG65 | UBB_PANTR | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG49 | UBB_MOUSE | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG47 | UBB_HUMAN | |
96.1 | Ubiquitin variant Ubv.21.4 | Q8MKD1 | UBB_HORSE | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG67 | UBB_GORGO | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG62 | UBB_CHICK | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG54 | UBB_CAVPO | |
96.1 | Ubiquitin variant Ubv.21.4 | P0CG53 | UBB_BOVIN | |
96.1 | Ubiquitin variant Ubv.21.4 | P68203 | RS27A_SPOFR | |
96.0 | Ubiquitin variant Ubv.21.4 | P62982 | RS27A_RAT | |
96.1 | Ubiquitin variant Ubv.21.4 | P68202 | RS27A_PLUXY | |
96.0 | Ubiquitin variant Ubv.21.4 | P62983 | RS27A_MOUSE | |
96.1 | Ubiquitin variant Ubv.21.4 | P29504 | RS27A_MANSE | |
96.0 | Ubiquitin variant Ubv.21.4 | P68200 | RS27A_ICTPU | |
96.0 | Ubiquitin variant Ubv.21.4 | P62979 | RS27A_HUMAN | |
96.1 | Ubiquitin variant Ubv.21.4 | P15357 | RS27A_DROME | |
96.0 | Ubiquitin variant Ubv.21.4 | P79781 | RS27A_CHICK | |
96.0 | Ubiquitin variant Ubv.21.4 | P62978 | RS27A_CAVPO | |
96.0 | Ubiquitin variant Ubv.21.4 | P62992 | RS27A_BOVIN | |
96.1 | Ubiquitin variant Ubv.21.4 | P0C276 | RL40_SHEEP | |
96.1 | Ubiquitin variant Ubv.21.4 | P62986 | RL40_RAT | |
96.1 | Ubiquitin variant Ubv.21.4 | P0C275 | RL40_PONPY | |
96.1 | Ubiquitin variant Ubv.21.4 | P63053 | RL40_PIG | |
96.1 | Ubiquitin variant Ubv.21.4 | P68205 | RL40_OPHHA | |
96.1 | Ubiquitin variant Ubv.21.4 | P62984 | RL40_MOUSE | |
96.1 | Ubiquitin variant Ubv.21.4 | P0C273 | RL40_MACFA | |
96.1 | Ubiquitin variant Ubv.21.4 | P62987 | RL40_HUMAN | |
96.1 | Ubiquitin variant Ubv.21.4 | P63052 | RL40_FELCA | |
96.1 | Ubiquitin variant Ubv.21.4 | P18101 | RL40_DROME | |
96.1 | Ubiquitin variant Ubv.21.4 | P63050 | RL40_CANLF | |
96.1 | Ubiquitin variant Ubv.21.4 | P63048 | RL40_BOVIN | |
95.0 | Ubiquitin-specific protease 2 (USP2) | O88623 | UBP2_MOUSE | |
95.5 | Ubiquitin-specific protease 2 (USP2) | Q2KHV7 | UBP2_BOVIN | |
95.5 | Ubiquitin-specific protease 2 (USP2) | Q5U349 | UBP2_RAT | |
99.4 | Ubiquitin-specific protease 2 (USP2) | O75604 | UBP2_HUMAN |