[대학원 생명과학과 세미나 안내]
연사 : 신동혁 박사(Institute of Biochemistry II, Goethe University-Medical Faculty)
연제 : Structural insights of phosphoribose dependent ubiquitination
일시 : 2018년 2월 14일 (수) 오전 11시
장소 : 하나과학관 A동 101호
초청교수 : 송현규 교수
Conventional ubiquitination regulates key cellular processes by utilizing the ATP-dependent formation of isopeptide bond between the ubiquitin (Ub) and primary amines in substrate proteins. Recently, bacterial effector proteins such as SdeA of pathogenic Legionella pneumophila, were shown to utilize NAD+ to mediate phosphoribosyl-linked ubiquitination (PR-ubiquitination) of serines in host substrate proteins. We determined the crystal structure of the catalytic core of SdeA, which contains a mono-ADP-ribosyl transferase (mART) and a phoshodiesterase (PDE) domain, and shed light on activity of two distinct catalytic sites for serine ubiquitination. The mART catalytic site is composed of an alpha-helical lobe (AHL) that together with the mART-core creates a chamber for NAD+ binding and ADP-ribosylation of Ub. Surprisingly, in our crystal structure the AHL has no physical proximity to the mART-core unlike in the structures of other bacterial ADP-ribosylating enzymes where it is an integral part of the mART domain and contributes to NAD+ binding and ADP-ribosylation of the substrate. Biochemical assays with small-angle X-ray scattering analysis suggest conformational shift of AHL to mART-core. We found that C-terminal region of SdeA stabilizes proximal form of AHL, while binding of NAD+ molecule itself is not sufficient to force AHL intact in mART-core. Our structure of SdeA give us to understand atomic details of PR-ubiquitination by the SidE family of bacterial enzymes.