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P22 c2 repressor-operator complex: mechanisms of direct and indirect readout.
Biochemistry. 2008 Feb 26; 47(8):2325-38.B

Abstract

The P22 c2 repressor protein (P22R) binds to DNA sequence-specifically and helps to direct the temperate lambdoid bacteriophage P22 to the lysogenic developmental pathway. We describe the 1.6 A X-ray structure of the N-terminal domain (NTD) of P22R in a complex with a DNA fragment containing the synthetic operator sequence [d(ATTTAAGATATCTTAAAT)]2. This operator has an A-T base pair at position 9L and a T-A base pair at position 9R and is termed DNA9T. Direct readout: nondirectional van der Waals interactions between protein and DNA appear to confer sequence-specificity. The structure of the P22R NTD-DNA9T complex suggests that sequence-specificity arises substantially from lock-and-key interaction of a valine with a complementary binding cleft on the major groove surface of DNA9T. The cleft is formed by four methyl groups on sequential base pairs of 5'-TTAA-3'. The valine cleft is intrinsic to the DNA sequence and does not arise from protein-induced DNA conformational changes. Protein-DNA hydrogen bonding plays a secondary role in specificity. Indirect readout: it is known that the noncontacted bases in the center of the complex are important determinants of affinity. The protein induces a transition of the noncontacted region from B-DNA to B'-DNA. The B' state is characterized by a narrow minor groove and a zigzag spine of hydration. The free energy of the transition from B- to B'-DNA is known to depend on the sequence. Thus, the observed DNA conformation and hydration allows for the formulation of a predictive model of the indirect readout phenomenon.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Watkins D
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, USA.
Hsiao C
No affiliation info available
Woods KK
No affiliation info available
Koudelka GB
No affiliation info available
Williams LD
No affiliation info available

MeSH

Base PairingBase SequenceBinding SitesBiosensing TechniquesCrystallography, X-RayDNADNA-Binding ProteinsModels, MolecularNucleic Acid ConformationProtein BindingProtein Structure, TertiaryRepressor ProteinsSubstrate SpecificityWater

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18237194

Citation

Watkins, Derrick, et al. "P22 C2 Repressor-operator Complex: Mechanisms of Direct and Indirect Readout." Biochemistry, vol. 47, no. 8, 2008, pp. 2325-38.
Watkins D, Hsiao C, Woods KK, et al. P22 c2 repressor-operator complex: mechanisms of direct and indirect readout. Biochemistry. 2008;47(8):2325-38.
Watkins, D., Hsiao, C., Woods, K. K., Koudelka, G. B., & Williams, L. D. (2008). P22 c2 repressor-operator complex: mechanisms of direct and indirect readout. Biochemistry, 47(8), 2325-38. https://doi.org/10.1021/bi701826f
Watkins D, et al. P22 C2 Repressor-operator Complex: Mechanisms of Direct and Indirect Readout. Biochemistry. 2008 Feb 26;47(8):2325-38. PubMed PMID: 18237194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P22 c2 repressor-operator complex: mechanisms of direct and indirect readout. AU - Watkins,Derrick, AU - Hsiao,Chiaolong, AU - Woods,Kristen Kruger, AU - Koudelka,Gerald B, AU - Williams,Loren Dean, Y1 - 2008/02/01/ PY - 2008/2/2/pubmed PY - 2008/5/7/medline PY - 2008/2/2/entrez SP - 2325 EP - 38 JF - Biochemistry JO - Biochemistry VL - 47 IS - 8 N2 - The P22 c2 repressor protein (P22R) binds to DNA sequence-specifically and helps to direct the temperate lambdoid bacteriophage P22 to the lysogenic developmental pathway. We describe the 1.6 A X-ray structure of the N-terminal domain (NTD) of P22R in a complex with a DNA fragment containing the synthetic operator sequence [d(ATTTAAGATATCTTAAAT)]2. This operator has an A-T base pair at position 9L and a T-A base pair at position 9R and is termed DNA9T. Direct readout: nondirectional van der Waals interactions between protein and DNA appear to confer sequence-specificity. The structure of the P22R NTD-DNA9T complex suggests that sequence-specificity arises substantially from lock-and-key interaction of a valine with a complementary binding cleft on the major groove surface of DNA9T. The cleft is formed by four methyl groups on sequential base pairs of 5'-TTAA-3'. The valine cleft is intrinsic to the DNA sequence and does not arise from protein-induced DNA conformational changes. Protein-DNA hydrogen bonding plays a secondary role in specificity. Indirect readout: it is known that the noncontacted bases in the center of the complex are important determinants of affinity. The protein induces a transition of the noncontacted region from B-DNA to B'-DNA. The B' state is characterized by a narrow minor groove and a zigzag spine of hydration. The free energy of the transition from B- to B'-DNA is known to depend on the sequence. Thus, the observed DNA conformation and hydration allows for the formulation of a predictive model of the indirect readout phenomenon. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/18237194/P22_c2_repressor_operator_complex:_mechanisms_of_direct_and_indirect_readout_ DB - PRIME DP - Unbound Medicine ER -