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Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein
- Publication Year :
- 2005
- Publisher :
- National Academy of Sciences, 2005.
-
Abstract
- Werner syndrome (WS) is an autosomal recessive disease that results in premature aging. Mutations in the WS gene ( WRN ) result in a loss of expression of the WRN protein and predispose WS patients to accelerated aging. As a helicase and a nuclease, WRN is unique among the five human RecQ helicase family members and is capable of multiple functions involved in DNA replication, repair, recombination, and telomere maintenance. A 144-residue fragment of WRN was previously determined to be a multifunctional DNA- and protein-binding domain (DPBD) that interacts with structure-specific DNA and a variety of DNA-processing proteins. In addition, DPBD functions as a nucleolar targeting sequence of WRN. The solution structure of the DPBD, the first of a WRN fragment, has been solved by NMR. DPBD consists of a winged helix-like motif and an unstructured C-terminal region of ≈20 aa. The putative DNA-binding surface of DPBD has been identified by using known structural and biochemical data. Based on the structural data and on the biochemical data, we suggest a surface on the DPBD for interacting with other proteins. In this structural model, a single winged helix domain binds to both DNA and other proteins. Furthermore, we propose that DPBD functions as a regulatory domain to regulate the enzymatic activity of WRN and to direct cellular localization of WRN through protein–protein interaction.
- Subjects :
- Premature aging
Models, Molecular
congenital, hereditary, and neonatal diseases and abnormalities
Magnetic Resonance Spectroscopy
Werner Syndrome Helicase
RecQ helicase
Amino Acid Motifs
Molecular Sequence Data
Protein Structure, Secondary
Protein structure
medicine
Humans
Amino Acid Sequence
education
Cellular localization
Werner syndrome
Genetics
education.field_of_study
Multidisciplinary
Binding Sites
biology
RecQ Helicases
DNA replication
DNA Helicases
Helicase
nutritional and metabolic diseases
DNA
Biological Sciences
medicine.disease
Protein Structure, Tertiary
Enzyme Activation
Exodeoxyribonucleases
biology.protein
Sequence Alignment
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....fc4a8f917064fb184ad4c302b8894682