Structural anatomy of telomere OB proteins

Abstract

Telomere DNA-binding proteins protect the ends of chromosomes in eukaryotes. A subset of these proteins are constructed with one or more OB folds and bind with G+T-rich single-stranded DNA found at the extreme termini. The resulting DNA-OB protein complex interacts with other telomere components to coordinate critical telomere functions of DNA protection and DNA synthesis. While the first crystal and NMR structures readily explained protection of telomere ends, the picture of how single-stranded DNA becomes available to serve as primer and template for synthesis of new telomere DNA is only recently coming into focus. New structures of telomere OB fold proteins alongside insights from genetic and biochemical experiments have made significant contributions towards understanding how protein-binding OB proteins collaborate with DNA-binding OB proteins to recruit telomerase and DNA polymerase for telomere homeostasis. This review surveys telomere OB protein structures alongside highly comparable structures derived from replication protein A (RPA) components, with the goal of providing a molecular context for understanding telomere OB protein evolution and mechanism of action in protection and synthesis of telomere DNA.

Keywords::

• Telomere structural biology
• single-stranded DNA-binding proteins
• OB fold
• x-ray crystallography
• NMR
• intrinsically disordered protein regions
• molecular recognition
• allostery

Acknowledgements

I thank Isabel Gardett for constructive suggestions on organization and style, Kigen Curtice and Dr. Catherine Dy for reading of drafts, Dr. Douglas Theobald for explanations of Bayesian analysis, Dr. Gerda Saxer Quance for discussions about evolution, and Dr. Michael Horvath for suggestions regarding chi-squared significance tests.

Declaration of interest

The NIH supported a portion of this work (GM067994).

Editor: Michael M. Cox