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001-es BibID:	BIBFORM031427
035-os BibID:	PMID:19919153 WOS:000271272000005
Első szerző:	Tóth-Petróczy Ágnes
Cím:	Disordered tails of homeodomains facilitate DNA recognition by providing a trade-off between folding and specific binding / Ágnes Tóth-Petróczy, Istvan Simon, Monika Fuxreiter, Yaakov Levy
Dátum:	2009
ISSN:	0002-7863
Megjegyzések:	DNA binding specificity of homeodomain transcription factors is critically affected by disordered N-terminal tails (N-tails) that undergo a disorder-to-order transition upon interacting with DNA. The mechanism of the binding process and the molecular basis of selectivity are largely unknown. The coupling between folding and DNA binding of Antp and NK-2 homeodomains was investigated by coarse-grained molecular dynamics simulations using the native protein-DNA complex. The disordered N-tails were found to decrease the stability of the free proteins by competing with the native intramolecular interactions and increasing the radius of gyration of the homeodomain cores. In the presence of DNA, however, the N-tails increase the stability of the homeodomains by reducing the coupling between folding and DNA binding. Detailed studies on Antp demonstrate that the N-tail anchors the homeodomain to DNA and accelerates formation of specific interactions all along the protein-DNA interface. The tidal electrostatic forces between the N-tail and DNA induce faster and tighter binding of the homeodomain core to the DNA; this mechanism conforms to a fly-casting mechanism. In agreement with experiments, the N-tail of Antp also improves the binding affinity for DNA, with a major contribution by the released waters. These results imply that varying the degree of folding upon binding and thereby modulating the size of the buried surface-disordered N-tails of homeodomains can fine-tune the binding strength for specific DNA sequences. Overall, both the kinetics and thermodynamics of specific DNA binding by homeodomains can be improved by N-tails using a mechanism that is inherent in their disordered state.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Journal of the American Chemical Society. - 131 : 42 (2009), p. 15084-15085. -
További szerzők:	Simon István Fuxreiter Mónika (1969-) (kutató vegyész) Levy, Yaakov
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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