Structure and function of the C-terminal PABC domain of human poly(A)-binding protein
- Guennadi Kozlov*,†,
- Jean-François Trempe*,†,
- Kianoush Khaleghpour*,‡,
- Avak Kahvejian*,
- Irena Ekiel§, and
- Kalle Gehring*,†,¶
- *Department of Biochemistry, McGill University and †Montreal Joint Center for Structural Biology, 3655 Promenade Sir William Osler, Montreal, QC, Canada H3G 1Y6; and §Pharmaceutical Biotechnology and Montreal Joint Center for Structural Biology, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, QC, Canada H4P 2R2
-
Edited by Roger D. Kornberg, Stanford University School of Medicine, Stanford, CA, and approved February 7, 2001 (received for review January 16, 2001)
Abstract
We have determined the solution structure of the C-terminal quarter of human poly(A)-binding protein (hPABP). The protein fragment contains a protein domain, PABC [for poly(A)-binding protein C-terminal domain], which is also found associated with the HECT family of ubiquitin ligases. By using peptides derived from PABP interacting protein (Paip) 1, Paip2, and eRF3, we show that PABC functions as a peptide binding domain. We use chemical shift perturbation analysis to identify the peptide binding site in PABC and the major elements involved in peptide recognition. From comparative sequence analysis of PABC-binding peptides, we formulate a preliminary PABC consensus sequence and identify human ataxin-2, the protein responsible for type 2 spinocerebellar ataxia (SCA2), as a potential PABC ligand.
Footnotes
-
↵ ‡ Present address: Pharmaceutical Biotechnology, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, QC, Canada H4P 2R2.
-
↵ ¶ To whom reprint requests should be addressed at the temporary address: Unité de Biochimie Structurale, Institut Pasteur, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2185, 25 Rue du Dr. Roux, 75724 Paris Cedex 15, France. E-mail: kalle{at}bri.nrc.ca.
-
This paper was submitted directly (Track II) to the PNAS office.
-
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID code 1G9L). The NMR assignments have been deposited in the BioMagResBank, www.bmrb.wisc.edu (accession no. 4915).
-
See commentary on page 4288.
- Abbreviations:
- PABC,
- poly(A)-binding protein C-terminal domain;
- hPABP,
- human poly(A)- binding protein;
- Paip,
- poly(A)-binding protein interacting protein;
- RRM,
- RNA recognition motif;
- NOESY,
- nuclear Overhauser effect spectroscopy;
- GST,
- glutathione S-transferase
- Copyright © 2001, The National Academy of Sciences
