Unknown

Dataset Information

0

Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites.


ABSTRACT: Poly(ADP-ribose) polymerase 1 (PARP1) synthesizes poly(ADP-ribose) (PAR) using nicotinamide adenine dinucleotide (NAD) as a substrate. Despite intensive research on the cellular functions of PARP1, the molecular mechanism of PAR formation has not been comprehensively understood. In this study, we elucidate the molecular mechanisms of poly(ADP-ribosyl)ation and identify PAR acceptor sites. Generation of different chimera proteins revealed that the amino-terminal domains of PARP1, PARP2 and PARP3 cooperate tightly with their corresponding catalytic domains. The DNA-dependent interaction between the amino-terminal DNA-binding domain and the catalytic domain of PARP1 increased V(max) and decreased the K(m) for NAD. Furthermore, we show that glutamic acid residues in the auto-modification domain of PARP1 are not required for PAR formation. Instead, we identify individual lysine residues as acceptor sites for ADP-ribosylation. Together, our findings provide novel mechanistic insights into PAR synthesis with significant relevance for the different biological functions of PARP family members.

SUBMITTER: Altmeyer M 

PROVIDER: S-EPMC2699514 | BioStudies | 2009-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5861426 | BioStudies
| S-EPMC7048826 | BioStudies
1000-01-01 | S-EPMC5100588 | BioStudies
2018-01-01 | S-EPMC5843604 | BioStudies
2011-01-01 | S-EPMC3041075 | BioStudies
2019-01-01 | S-EPMC6478412 | BioStudies
1000-01-01 | S-EPMC2722505 | BioStudies
1000-01-01 | S-EPMC4626836 | BioStudies
2015-01-01 | S-EPMC4680915 | BioStudies
2012-01-01 | S-EPMC3527939 | BioStudies