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Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 Å resolution

KH (hnRNP K homology) domains, consisting of ∼70 amino acid residues, are present in a variety of nucleic-acid-binding proteins. Among these are poly(C)-binding proteins (PCBPs), which are important regulators of mRNA stability and posttranscriptional regulation in general. All PCBPs contain three d...

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Autores principales: Fenn, Sebastian, Du, Zhihua, Lee, John K., Tjhen, Richard, Stroud, Robert M., James, Thomas L.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885661/
https://www.ncbi.nlm.nih.gov/pubmed/17426136
http://dx.doi.org/10.1093/nar/gkm139
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author Fenn, Sebastian
Du, Zhihua
Lee, John K.
Tjhen, Richard
Stroud, Robert M.
James, Thomas L.
author_facet Fenn, Sebastian
Du, Zhihua
Lee, John K.
Tjhen, Richard
Stroud, Robert M.
James, Thomas L.
author_sort Fenn, Sebastian
collection PubMed
description KH (hnRNP K homology) domains, consisting of ∼70 amino acid residues, are present in a variety of nucleic-acid-binding proteins. Among these are poly(C)-binding proteins (PCBPs), which are important regulators of mRNA stability and posttranscriptional regulation in general. All PCBPs contain three different KH domains and recognize poly(C)-sequences with high affinity and specificity. To reveal the molecular basis of poly(C)-sequence recognition, we have determined the crystal structure, at 1.6 Å resolution, of PCBP2 KH3 domain in complex with a 7-nt DNA sequence (5′-AACCCTA-3′) corresponding to one repeat of the C-rich strand of human telomeric DNA. The domain assumes a type-I KH fold in a βααββα configuration. The protein–DNA interface could be studied in unprecedented detail and is made up of a series of direct and water-mediated hydrogen bonds between the protein and the DNA, revealing an especially dense network involving several structural water molecules for the last 2 nt in the core recognition sequence. Unlike published KH domain structures, the protein crystallizes without protein–protein contacts, yielding new insights into the dimerization properties of different KH domains. A nucleotide platform, an interesting feature found in some RNA molecules, was identified, evidently for the first time in DNA.
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spelling pubmed-18856612007-06-07 Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 Å resolution Fenn, Sebastian Du, Zhihua Lee, John K. Tjhen, Richard Stroud, Robert M. James, Thomas L. Nucleic Acids Res Structural Biology KH (hnRNP K homology) domains, consisting of ∼70 amino acid residues, are present in a variety of nucleic-acid-binding proteins. Among these are poly(C)-binding proteins (PCBPs), which are important regulators of mRNA stability and posttranscriptional regulation in general. All PCBPs contain three different KH domains and recognize poly(C)-sequences with high affinity and specificity. To reveal the molecular basis of poly(C)-sequence recognition, we have determined the crystal structure, at 1.6 Å resolution, of PCBP2 KH3 domain in complex with a 7-nt DNA sequence (5′-AACCCTA-3′) corresponding to one repeat of the C-rich strand of human telomeric DNA. The domain assumes a type-I KH fold in a βααββα configuration. The protein–DNA interface could be studied in unprecedented detail and is made up of a series of direct and water-mediated hydrogen bonds between the protein and the DNA, revealing an especially dense network involving several structural water molecules for the last 2 nt in the core recognition sequence. Unlike published KH domain structures, the protein crystallizes without protein–protein contacts, yielding new insights into the dimerization properties of different KH domains. A nucleotide platform, an interesting feature found in some RNA molecules, was identified, evidently for the first time in DNA. Oxford University Press 2007-04 2007-04-10 /pmc/articles/PMC1885661/ /pubmed/17426136 http://dx.doi.org/10.1093/nar/gkm139 Text en © 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Fenn, Sebastian
Du, Zhihua
Lee, John K.
Tjhen, Richard
Stroud, Robert M.
James, Thomas L.
Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 Å resolution
title Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 Å resolution
title_full Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 Å resolution
title_fullStr Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 Å resolution
title_full_unstemmed Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 Å resolution
title_short Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 Å resolution
title_sort crystal structure of the third kh domain of human poly(c)-binding protein-2 in complex with a c-rich strand of human telomeric dna at 1.6 å resolution
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885661/
https://www.ncbi.nlm.nih.gov/pubmed/17426136
http://dx.doi.org/10.1093/nar/gkm139
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