Structural Insights into E1-Catalyzed Ubiquitin Activation and Transfer to Conjugating Enzymes

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Cell

DOI:https://doi.org/10.1016/j.cell.2008.05.046· OSTI ID:959561

Lee, I; Schindelin, H

Ubiquitin (Ub) and ubiquitin-like proteins (Ubls) are conjugated to their targets by specific cascades involving three classes of enzymes, E1, E2, and E3. Each E1 adenylates the C terminus of its cognate Ubl, forms a E1{approx}Ubl thioester intermediate, and ultimately generates a thioester-linked E2{approx}Ubl product. We have determined the crystal structure of yeast Uba1, revealing a modular architecture with individual domains primarily mediating these specific activities. The negatively charged C-terminal ubiquitin-fold domain (UFD) is primed for binding of E2s and recognizes their positively charged first a helix via electrostatic interactions. In addition, a mobile loop from the domain harboring the E1 catalytic cysteine contributes to E2 binding. Significant, experimentally observed motions in the UFD around a hinge in the linker connecting this domain to the rest of the enzyme suggest a conformation-dependent mechanism for the transthioesterification function of Uba1; however, this mechanism clearly differs from that of other E1 enzymes.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959561
• Report Number(s): BNL--82547-2009-JA
• Journal Information: Cell, Journal Name: Cell Journal Issue: 2 Vol. 134; ISSN 0092-8674; ISSN CELLB5
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ARCHITECTURE
CRYSTAL STRUCTURE
CYSTEINE
ELECTROSTATICS
ENZYMES
PROTEINS
TARGETS
YEASTS
national synchrotron light source