3TDU

N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex: Structure of a human Cul1WHB-Dcn1P-acetylated Ubc12N complex

Summary for 3TDU

• Entry DOI: 10.2210/pdb3tdu/pdb
• Related: 3TDI 3TDZ
• Descriptor: DCN1-like protein 1, Cullin-1, NEDD8-conjugating enzyme Ubc12, ... (4 entities in total)
• Functional Keywords: e2:e3, ligase-protein binding complex, ligase/protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 68324.90

Authors

Scott, D.C.,Monda, J.K.,Bennett, E.J.,Harper, J.W.,Schulman, B.A. (deposition date: 2011-08-11, release date: 2011-10-12, Last modification date: 2024-11-27)

Primary citation

Scott, D.C.,Monda, J.K.,Bennett, E.J.,Harper, J.W.,Schulman, B.A.
N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex.
Science, 334:674-678, 2011

PubMed Abstract: Although many eukaryotic proteins are amino (N)-terminally acetylated, structural mechanisms by which N-terminal acetylation mediates protein interactions are largely unknown. Here, we found that N-terminal acetylation of the E2 enzyme, Ubc12, dictates distinctive E3-dependent ligation of the ubiquitin-like protein Nedd8 to Cul1. Structural, biochemical, biophysical, and genetic analyses revealed how complete burial of Ubc12's N-acetyl-methionine in a hydrophobic pocket in the E3, Dcn1, promotes cullin neddylation. The results suggest that the N-terminal acetyl both directs Ubc12's interactions with Dcn1 and prevents repulsion of a charged N terminus. Our data provide a link between acetylation and ubiquitin-like protein conjugation and define a mechanism for N-terminal acetylation-dependent recognition.

PubMed: 21940857
DOI: 10.1126/science.1209307

Experimental method

X-RAY DIFFRACTION (1.5 Å)