2le0

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2le0, 10 NMR models ()
Gene: Parp1, Adprt (Rattus norvegicus)
Activity: NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

PARP BRCT Domain

Publication Abstract from PubMed

ABSTRACT: BACKGROUND: Poly(ADP-ribose) polymerase-1 (PARP-1) is one of the first proteins localized to foci of DNA damage. Upon activation by encountering nicked DNA, the PARP-1 mediated trans-poly(ADP-ribosyl)ation of DNA binding proteins occurs, facilitating access and accumulation of DNA repair factors. PARP-1 also auto-(ADP-ribosyl)ates its central BRCT-containing domain forming part of an interaction site for the DNA repair scaffolding protein X-ray cross complementing group 1 protein (XRCC1). The co-localization of XRCC1, as well as bound DNA repair factors, to sites of DNA damage is important for cell survival and genomic integrity. RESULTS: Here we present the solution structure and biophysical characterization of the BRCT domain of rat PARP-1. The PARP-1 BRCT domain has the globular alpha/beta fold characteristic of BRCT domains and has a thermal melting transition of 43.0 degrees C. In contrast to a previous characterization of this domain, we demonstrate that it is monomeric in solution using both gel-filtration chromatography and small-angle X-ray scattering. Additionally, we report that the first BRCT domain of XRCC1 does not interact significantly with the PARP-1 BRCT domain in the absence of ADP-ribosylation. Moreover, none of the interactions with other longer PARP-1 constructs which previously had been demonstrated in a pull-down assay of mammalian cell extracts were detected. CONCLUSIONS: The PARP-1 BRCT domain has the conserved BRCT fold that is known to be an important protein:protein interaction module in DNA repair and cell signalling pathways. Data indicating no significant protein:protein interactions between PARP-1 and XRCC1 likely results from the absence of poly(ADP-ribose) in one or both binding partners, and further implicates a poly(ADP-ribose)-dependent mechanism for localization of XRCC1 to sites of DNA damage.

Structural studies of the PARP-1 BRCT domain., Loeffler PA, Cuneo MJ, Mueller GA, Derose EF, Gabel SA, London RE, BMC Struct Biol. 2011 Oct 3;11:37. PMID:21967661

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2le0 is a 1 chain structure with sequence from Rattus norvegicus. Full experimental information is available from OCA.

See Also

Reference

  • Loeffler PA, Cuneo MJ, Mueller GA, Derose EF, Gabel SA, London RE. Structural studies of the PARP-1 BRCT domain. BMC Struct Biol. 2011 Oct 3;11:37. PMID:21967661 doi:10.1186/1472-6807-11-37

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