5IAA

Crystal structure of human UBA5 in complex with UFM1

Summary for 5IAA

• Entry DOI: 10.2210/pdb5iaa/pdb
• Descriptor: Ubiquitin-like modifier-activating enzyme 5, Ubiquitin-fold modifier 1, ZINC ION, ... (4 entities in total)
• Functional Keywords: ubiquitin like protein and e1, cell cycle
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : Q9GZZ9; Nucleus : P61960
• Total number of polymer chains: 4
• Total formula weight: 82405.25

Authors

Oweis, W.,Padala, P.,Wiener, R. (deposition date: 2016-02-21, release date: 2016-09-28, Last modification date: 2024-01-10)

Primary citation

Oweis, W.,Padala, P.,Hassouna, F.,Cohen-Kfir, E.,Gibbs, D.R.,Todd, E.A.,Berndsen, C.E.,Wiener, R.
Trans-Binding Mechanism of Ubiquitin-like Protein Activation Revealed by a UBA5-UFM1 Complex.
Cell Rep, 16:3113-3120, 2016

PubMed Abstract: Modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is a critical cellular process implicated in a variety of cellular states and outcomes. A prerequisite for target protein modification by a UBL is the activation of the latter by activating enzymes (E1s). Here, we present the crystal structure of the non-canonical homodimeric E1, UBA5, in complex with its cognate UBL, UFM1, and supporting biochemical experiments. We find that UBA5 binds to UFM1 via a trans-binding mechanism in which UFM1 interacts with distinct sites in both subunits of the UBA5 dimer. This binding mechanism requires a region C-terminal to the adenylation domain that brings UFM1 to the active site of the adjacent UBA5 subunit. We also find that transfer of UFM1 from UBA5 to the E2, UFC1, occurs via a trans mechanism, thereby requiring a homodimer of UBA5. These findings explicitly elucidate the role of UBA5 dimerization in UFM1 activation.

PubMed: 27653677
DOI: 10.1016/j.celrep.2016.08.067

Experimental method

X-RAY DIFFRACTION (1.85 Å)