Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2-activating Protein*

AUTOR(ES)

Fu, Qing-Shan

FONTE

American Society for Biochemistry and Molecular Biology

RESUMO

Ubiquitin (Ub) is an essential modifier conserved in all eukaryotes from yeast to human. Phospholipase A2-activating protein (PLAA), a mammalian homolog of yeast DOA1/UFD3, has been proposed to be able to bind with Ub, which plays important roles in endoplasmic reticulum-associated degradation, vesicle formation, and DNA damage response. We have identified a core domain from the PLAA family ubiquitin-binding region of human PLAA (residues 386–465, namely PFUC) that can bind Ub and elucidated its solution structure and Ub-binding mode by NMR approaches. The PFUC domain possesses equal population of two conformers in solution by cis/trans-isomerization, whereas the two isomers exhibit almost equivalent Ub binding abilities. This domain structure takes a novel fold consisting of four β-strands and two α-helices, and the Ub-binding site on PFUC locates in the surface of α2-helix, which is to some extent analogous to those of UBA, CUE, and UIM domains. This study provides structural basis and biochemical information for Ub recognition of the novel PFU domain from a PLAA family protein that may connect ubiquitination and degradation in endoplasmic reticulum-associated degradation.

Documentos Relacionados

• Cloning of a phospholipase A2-activating protein.
• Cholera toxin induces synthesis of phospholipase A2-activating protein.
• Structural basis for recognition of 2′,5′-linked oligoadenylates by human ribonuclease L
• Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor
• Structural basis of replication origin recognition by the DnaA protein