The arginine finger of the Bloom syndrome protein: its structural organization and its role in energy coupling
| Autor: | Mounira Amor-Guéret, Xu-Guang Xi, Pascal Rigolet, Ye Yang, Peng-Ye Wang, Shuo-Xing Dou, Hua Ren |
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| Přispěvatelé: | Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular congenital hereditary and neonatal diseases and abnormalities Arginine [SDV]Life Sciences [q-bio] Amino Acid Motifs Molecular Sequence Data Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Adenosine Triphosphate ATP hydrolysis Structural Biology Genetics medicine Bloom syndrome Amino Acid Sequence ComputingMilieux_MISCELLANEOUS 030304 developmental biology chemistry.chemical_classification Adenosine Triphosphatases 0303 health sciences RecQ Helicases DNA Helicases Helicase nutritional and metabolic diseases DNA medicine.disease Enzyme Biochemistry chemistry Bloom syndrome protein biology.protein Mutagenesis Site-Directed Vanadates Adenosine triphosphate 030217 neurology & neurosurgery |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2007, 35 (18), pp.6029-6041. ⟨10.1093/nar/gkm544⟩ Nucleic Acids Research, 2007, 35 (18), pp.6029-6041. ⟨10.1093/nar/gkm544⟩ |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | RecQ family helicases are essential in maintaining chromosomal DNA stability and integrity. Despite extensive studies, the mechanisms of these enzymes are still poorly understood. Crystal structures of many helicases reveal a highly conserved arginine residue located near the gamma-phosphate of ATP. This residue is widely recognized as an arginine finger, and may sense ATP binding and hydrolysis, and transmit conformational changes. We investigated the existence and role of the arginine finger in the Bloom syndrome protein (BLM), a RecQ family helicase, in ATP hydrolysis and energy coupling. Our studies by combination of structural modelling, site-directed mutagenesis and biochemical and biophysical approaches, demonstrate that mutations of residues interacting with the gamma-phosphate of ATP or surrounding the ATP-binding sites result in severe impairment in the ATPase activity of BLM. These mutations also impair BLM's DNA-unwinding activities, but do not affect its ATP and DNA-binding abilities. These data allow us to identify R982 as the residue that functions as a BLM arginine finger. Our findings further indicate how the arginine finger is precisely positioned by the conserved motifs with respect to the gamma-phosphate. |
| Databáze: | OpenAIRE |
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