A flexible interface between DNA ligase and PCNA supports conformational switching and efficient ligation of DNA

被引:135
作者
Pascal, John M.
Tsodikov, Oleg V.
Hura, Greg L.
Song, Wei
Cotner, Elizabeth A.
Classen, Scott
Tomkinson, Alan E.
Tainer, John A. [1 ]
Ellenberger, Tom
机构
[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[2] Univ Maryland, Sch Med, Radiat Oncol Res Lab, Dept Radiat Oncol, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA
[4] Lawrence Berkeley Lab, Div Life Sci, Dept Mol Biol, Berkeley, CA 94720 USA
[5] Scripps Res Inst, Skaggs Inst Chem Biol, Dept Mol Biol, La Jolla, CA 92037 USA
[6] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA
关键词
D O I
10.1016/j.molcel.2006.08.015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
DNA sliding clamps encircle DNA and provide binding sites for many DNA-processing enzymes. However, it is largely unknown how sliding clamps like proliferating cell nuclear antigen (PCNA) coordinate multistep DNA transactions. We have determined structures of Sulfolobus solfataricus DNA ligase and heterotrimeric PCNA separately by X-ray diffraction and in complex by small-angle X-ray scattering (SAXS). Three distinct PCNA subunits assemble into a protein ring resembling the homotrimeric PCNA of humans but with three unique protein-binding sites. In the absence of nicked DNA, the Sulfolobus solfataricus DNA ligase has an open, extended conformation. When complexed with heterotrimeric PCNA, the DNA ligase binds to the PCNA3 subunit and ligase retains an open, extended conformation. A closed, ring-shaped conformation of ligase catalyzes a DNA end-joining reaction that is strongly stimulated by PCNA. This open-to-closed switch in the conformation of DNA ligase is accommodated by a malleable interface with PCNA that serves as an efficient platform for DNA ligation.
引用
收藏
页码:279 / 291
页数:13
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