Function
UBA1's place in the Ubiquitination process, E1 what that means etc.
Structural highlights
The of Uba1 consists of six structural domains (IAD, AAD, FCCH, SCCH, 4HB, and UFD), four of which pack together to create a central canyon.{Lee, 2008} The canyon is divided into two distinct clefts (left and right) by the SCCH/AAD linker fragment.{Lee, 2008} Uba1 exists as a in solution, with two monomers interacting in a noncovalent manner. Ubiquitin binds to the cysteine located on the right cleft of Uba1 which allows for Ubiquitin to orient itself relative to the active site located on the left cleft.{Lee, 2008} The structure of results in a change in conformation that buries a significant portion of Uba1 exposed surface area.{Lee, 2008} The located on the SCCH domain of Uba1 forms a thioester with the C-terminus of Ubiquitin, forming a thioester complex.{Lee, 2008} It is suggested that a significant conformation change occurs when Ubiquitin binds to Uba1 due to the large distance (~35 Å) between the catalytic cysteine residue and the adenylation active site.{Lee, 2008; Walden, 2003} When Ubiquitin binds, Uba1 then coordinates the transfer of Ubiquitin onto an E2 enzyme.{Lee, 2008} A transthioesterfication of Ubiquitin from the catalytic cysteine of Uba1 to the catalytic cysteine of the E2 occurs when Uba1 and E2 interact.{Lee, 2008} The E2, in conjunction with the E3 enzyme, transfers the Ubiquitin onto its final substrate.
References
Lee I, Schindelin H. Structural Insights into E1-Catalyzed Ubiquitin Activation and Transfer to Conjugating Enzymes. Cell 134, 268–278 (2008).
Walden H, Podgorski MS, Huang DT, Miller DW, Howard RJ, Minor DL Jr, Holton JM, Schulman BA. The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Molecular Cell 12, 1427–1437 (2003).
