Sandbox Reserved 975

The SUMO-conjugating enzyme UBC9 is involved in ubiquitination of proteins.

The Ubiquitin is a small protein of 76 aa.

Ubiquitination is a post translationnal modification where an ubiquitin is attached to a protein. This modification has several consequences, it can lead to the degradation of the protein via the proteasome, it can change the protein localization or it can alter the interaction of the protein with other factors, this is why this modification plays an important role in the control of many cellular processes.

UBC9 in particular is important in the cell cycle progression because it allows the degradation of S phase and M phase cyclines.

Ubiquitination occurs in three steps : Activation performed by ubiquitin-activating enzymes E1, conjugation performed by ubiquitin-conjugating enzymes E2 and ligation performed by ubiquitin ligases E3.

During the first step the Ct Carboxyl group of the ubiquitin is linked to the cystein sulfhydryl group of E1.

The second step is a transesterification to transfer the active ubiquitin from the cystein of E1 to the cystein of E2. E2 binds the activated ubiquitin and E1.

During the third step E3 catalyses the formation of an isopeptide bond between a lysine of the substrate and a glycine of the ubiquitin.

UBC9 is a E2. It is a lynchpin in the SUMO pathway, it interacts with E1 during the activation, then with the ubiquitin after the transfer and finally with E3 during conjugation. It is particularly important for the formation of polymeric chain when the number of SUMO exceeds 2.

Structure

UBC9 is a monomer of 158 amino acids.

It is comprised of a single domain with α helices and β-sheets, typical of the core domain of the UBCs.

The dimensions of the surface are 20 Å X 30 Å X 50 Å.

The core domain contains an antiparallel β-sheet with 4 strand (β1 to β4, residues 25-30, 36-46, 57-63, 74-77)

And 4 αhelices (α1 to α4, residues 1-18, 109–121, 131-139, 141-154)

This secondary structure represent 50% of the polypetide (33% α-helices and 17% β-sheets)

There are two cis-prolines Pro69 and Pro79 that play an important role in the structure of the protein.

Function

Interaction with the substrates

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