NDLI: Proliferating Cell Nuclear Antigen (PCNA) Interactions in Solution Studied by NMR

Content Provider	PubMed Central
Author	De, Biasio Alfredo Ramón, Campos-olivas Sánchez, Ricardo López-alonso, Jorge P. David, Pantoja-uceda Merino, Nekane Villate, Maider Martin-garcia, Jose M. Castillo, Francisco Luque, Irene Blanco, Francisco J.
Editor	Pastore, Annalisa
Copyright Year	2012
Abstract	PCNA is an essential factor for DNA replication and repair. It forms a ring shaped structure of 86 kDa by the symmetric association of three identical protomers. The ring encircles the DNA and acts as a docking platform for other proteins, most of them containing the PCNA Interaction Protein sequence (PIP-box). We have used NMR to characterize the interactions of PCNA with several other proteins and fragments in solution. The binding of the PIP-box peptide of the cell cycle inhibitor p21 to PCNA is consistent with the crystal structure of the complex. A shorter p21 peptide binds with reduced affinity but retains most of the molecular recognition determinants. However the binding of the corresponding peptide of the tumor suppressor ING1 is extremely weak, indicating that slight deviations from the consensus PIP-box sequence dramatically reduce the affinity for PCNA, in contrast with a proposed less stringent PIP-box sequence requirement. We could not detect any binding between PCNA and the MCL-1 or the CDK2 protein, reported to interact with PCNA in biochemical assays. This suggests that they do not bind directly to PCNA, or they do but very weakly, with additional unidentified factors stabilizing the interactions in the cell. Backbone dynamics measurements show three PCNA regions with high relative flexibility, including the interdomain connector loop (IDCL) and the C-terminus, both of them involved in the interaction with the PIP-box. Our work provides the basis for high resolution studies of direct ligand binding to PCNA in solution.
Related Links	http://dx.doi.org/10.1371/journal.pone.0048390
Starting Page	48390
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	7
Language	English
Publisher	Public Library of Science
Publisher Date	2012-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Correction: Proliferating Cell Nuclear Antigen (PCNA) Interactions in Solution Studied by NMR

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Correction: Proliferating Cell Nuclear Antigen (PCNA) Interactions in Solution Studied by NMR

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