Crystal structure of the cyclin-specific ubiquitin-conjugating enzyme fromclam, E2-C, at 2.0 angstrom resolution

The destruction of the cyclin B protein is necessary for the cell to exit f rom mitosis. The destruction of cyclin B occurs via the ubiquitin/proteasom e system and involves a specific ubiquitin-conjugating enzyme (Ubc) that do nates ubiquitin to cyclin B. Here we present the crystal structure of the c yclin-specific Ubc from clam, E2-C, determined at 2.0 Angstrom resolution. The E2-C enzyme contains an N-terminal extension in addition to the Ubc cor e domain. The N-terminal extension is disordered, perhaps reflecting a need for flexibility as it interacts with various partners in the ubiquitinatio n system. The overall structure of the E2-C core domain is quite similar to those in previously determined Ubc proteins. The interaction between parti cular pairs of E2-C proteins in the crystal has some of the hallmarks of a functional dimer, though solution studies suggest that the E2-C protein exi sts as a monomer. Comparison of the E2-C structure with that of the other a vailable Ubc structures indicates conserved surface residues that may inter act with common components of the ubiquitination system. Such comparison al so reveals a remarkable spine of conserved hydrophobic residues in the cent er of the protein that may drive the protein to fold and stabilize the prot ein once folded. Comparison of residues conserved only among E2-C and its h omologues indicates surface areas that may be involved in mitotic-specific ubiquitination.