7OK7

Crystal structure of the UNC119B ARL3 complex

Summary for 7OK7

• Entry DOI: 10.2210/pdb7ok7/pdb
• Descriptor: ADP-ribosylation factor-like protein 3, Protein unc-119 homolog B, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (8 entities in total)
• Functional Keywords: complex, g-protein, protein transport
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 12
• Total formula weight: 258374.50

Authors

Yelland, T.,Ismail, S. (deposition date: 2021-05-17, release date: 2021-06-09, Last modification date: 2024-01-31)

Primary citation

Yelland, T.,Garcia, E.,Samarakoon, Y.,Ismail, S.
The Structural and Biochemical Characterization of UNC119B Cargo Binding and Release Mechanisms.
Biochemistry, 60:1952-1963, 2021

PubMed Abstract: Two paralogs of the guanine dissociation inhibitor-like solubilizing factors UNC119, UNC119A and UNC119B, are present in the human genome. UNC119 binds to N-myristoylated proteins and masks the hydrophobic lipid from the hydrophilic cytosol, facilitating trafficking between different membranes. Two classes of UNC119 cargo proteins have been classified: low affinity cargoes, released by the Arf-like proteins ARL2 and ARL3, and high affinity cargoes, which are specifically released by ARL3 and trafficked to either the primary cilium or the immunological synapse. The UNC119 homologues have reported differences in functionality, but the structural and biochemical bases for these differences are unknown. Using myristoylated peptide binding and release assays, we show that peptides sharing the previously identified UNC119A high affinity motif show significant variations of binding affinities to UNC119B of up to 427-fold. Furthermore, we solve the first two crystal structures of UNC119B, one in complex with the high affinity cargo peptide of LCK and a second one in complex with the release factor ARL3. Using these novel structures, we identify a stretch of negatively charged amino acids unique to UNC119B that may undergo a conformational change following binding of a release factor which we propose as an additional release mechanism specific to UNC119B.

PubMed: 34130453
DOI: 10.1021/acs.biochem.1c00251

Experimental method

X-RAY DIFFRACTION (3.15 Å)