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.

Nonspecific Recognition Is Achieved in Pot1pC through the Use of Multiple Binding Modes

“…1A). This surface includes β-strands β1–β5 and is centered on strands β2 and β3(Theobald et al, 2003; Horvath, 2011). The OB-fold differs from most in that it contains an extended loop between β2 and β3 (L23) and a sixth β-strand that creates an additional loop (L56).…”

Coordinated Interactions of Multiple POT1-TPP1 Proteins with Telomere DNA

“…In all eukaryotes, the 3Ј tails of telomeres end in single-stranded DNA overhangs that are recognized by POT1-or POT1-like proteins (49). Structurally, these proteins contain conserved oligonucleotide/oligosaccharide binding fold motifs that are involved in ssDNA recognition and specificity (50,51). Recent evidence shows that full-length Schizosaccharomyces pombe POT1 molecules bind telomeric DNA repeats as a dimer (52).…”

A popular engagement at the ends

“…Notably, these two structural elements are in close physical proximity, suggesting a single contiguous surface for binding telomerase (named TEL patch by Nandakumar et al). Also noteworthy is the fact this particular facet of the OB fold is distinct from the canonical DNA-binding surface of OB folds, and appears to be infrequently used for binding proteins 15 . With regard to the telomerase-side of the protein-protein interface, previous studies suggest the involvement of the TEN domain, an N-terminal DNA-binding domain of TERT that is believed to “anchor” telomerase to telomere DNA during processive synthesis 16, 17 .…”