Parkin
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
| - | Clicking <scene name='81/817543/All_pk_domains/3'>here</scene> will highlight each domain of Parkin by color. | + | Parkin's <scene name='81/817545/Secondary_structure/1'>secondary structure</scene> reveals a compact, autoinhibited conformation. <scene name='81/817545/Ubl_secondary/1'>Ubl domain</scene> is made of 5 strands and 2 helices; <scene name='81/817545/Ring0_secondary_structure/1'>RING0 domain</scene> contains 1 helix and 5 strands; <scene name='81/817545/Ring1_secondary_structure/1'>RING1 domain</scene> is made of 5 strands and 2 helices; The <scene name='81/817545/Ibr_secondary_structure/1'>IBR domain</scene> is composed solely of 3 beta strands; the <scene name='81/817545/Rep_secondary_structure/1'>REP element</scene> consists of an alpha-helix; and the <scene name='81/817545/Ring2_secondary_structure/1'>RING2 domain</scene> is made of 1 alpha-helix and 4 beta-strands. Clicking <scene name='81/817543/All_pk_domains/3'>here</scene> will highlight each domain of Parkin by color. |
Parkin is a monomeric 465-residues long protein containing an <span style="color:green">'''Ubiquitin-like (Ubl)'''</span> domain, a <span style="color:blue">'''RING0'''</span> domain, a <span style="color:purple">'''RING1'''</span> domain, an <span style="color:black">'''In Between Rings (IBR)'''</span> domain, a <span style="color:red">'''repressor (REP)'''</span> element and a <span style="color:brown">'''RING2'''</span> domain. Parkin is produced by the cell in an autoinhibited state. The <scene name='81/818543/Ubl/1'>Ubl domain</scene> maintains a compact <scene name='81/817543/Ring0-ring1/2'>RING0-RING1 interface</scene>, and together with the REP element, , prevents the E2 from binding to the RING1 domain. Phosphorylation of the <scene name='81/817543/Ser65_pk/3'>Ser65 residue</scene> in the Ubl domain leads to a change in conformation in the tertiary structure of the protein in the RING0-RING1 interface, which is optimized for pUb binding. However, both pUb and pUbl cannot be bound to parkin at the same time, which is consistent with the proposed allosteric loss of structure to the C-terminus of Helix H3 and IBR domain that would interfere with the Ubl-binding site. | Parkin is a monomeric 465-residues long protein containing an <span style="color:green">'''Ubiquitin-like (Ubl)'''</span> domain, a <span style="color:blue">'''RING0'''</span> domain, a <span style="color:purple">'''RING1'''</span> domain, an <span style="color:black">'''In Between Rings (IBR)'''</span> domain, a <span style="color:red">'''repressor (REP)'''</span> element and a <span style="color:brown">'''RING2'''</span> domain. Parkin is produced by the cell in an autoinhibited state. The <scene name='81/818543/Ubl/1'>Ubl domain</scene> maintains a compact <scene name='81/817543/Ring0-ring1/2'>RING0-RING1 interface</scene>, and together with the REP element, , prevents the E2 from binding to the RING1 domain. Phosphorylation of the <scene name='81/817543/Ser65_pk/3'>Ser65 residue</scene> in the Ubl domain leads to a change in conformation in the tertiary structure of the protein in the RING0-RING1 interface, which is optimized for pUb binding. However, both pUb and pUbl cannot be bound to parkin at the same time, which is consistent with the proposed allosteric loss of structure to the C-terminus of Helix H3 and IBR domain that would interfere with the Ubl-binding site. | ||
Revision as of 23:44, 16 June 2019
Parkin
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References
Kumar, A., Aguirre, J.D., Condos, T.E., Martinez-Torres, R.J., Chaugule, V.K., Toth, R., Sundaramoorthy, R., Mercier, P., Knebel, A., Spratt, D.E., Barber, K.R., Shaw, G.S., Walden, H. Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis. (2015) Embo J. 34: 2506-2521 Duplan , E., Sevalle, J., Viotti, J., Goiranm T., Bauer, C., Renbaum, P., Levy-Lahad, E., Gautier, C. A., Corti, O., Leroudier, N., Checler, F., da Costa, C. A. (2013) Parkin differently regulates Presenilin-1 and Presenilin-2 functions by direct control of their promoter transcription. J. Mol. Biol. 5, 132-142.
