The recognition of single-stranded DNA (ssDNA) is integral to myriad cellular

The recognition of single-stranded DNA (ssDNA) is integral to myriad cellular functions. and processing of single-stranded DNA (ssDNA) require a diverse set LEE011 reversible enzyme inhibition of binding proteins. Each instance of ssDNA must be managed appropriately and its aberrant presence acknowledged and resolved in an efficient manner. Inappropriate recognition or processing of ssDNA can result in chromosomal damage leading to cancer, senescence, or cell death. ssDNA-binding proteins have a wide range of structures and functions, but many of them contain small autonomous domains whose recognition of ssDNA has been well studied. These domains include four structural topologies that have been structurally characterized with ssDNA: oligonucleotide/oligosaccharide/oligopeptide-binding (OB) folds, K homology (KH) domains, RNA recognition motifs (RRMs), and whirly domains. In this review, we review these domains and how they bind ssDNA. Additionally, we describe the way in which they accomplish or avoid specificity with respect to both DNA sequence and ssRNA. Finally, we describe how these domains work together to fulfill their pleiotropic roles. A comprehensive description of all proteins known to interact with ssDNA is outside of the scope of this review; due to space limitations, we have excluded many interesting systems that interact with ssDNA in other contexts. We direct the reader to other sources for insights into proteins that bind both dsDNA and ssDNA (Chen et al., 2008; Duderstadt et al., 2011; Huang et al., 2012), interact with ssDNA transiently (de Silva et al., 2009; Itsathitphaisarn et al., 2012; Zhang et al., 2012), utilize double-stranded shape to aid in recognition (Barabas et al., 2008; Boer et al., 2006; Messing et al., 2012; Zhang et al., 2012), and bind only one or two nucleotides (Eastberg et al., 2004; Jaudzems et al., 2012). We have also excluded proteins that lack a high-resolution bound structure. OB Folds OB folds are multifunctional domains found in many areas of biology (reviewed in Murzin, 1993; Theobald et al., 2003) (Physique 1A). Because this fold is usually notoriously hard to predict from main sequence, the full representation of these domains in the proteome continues to be unidentified. OB folds are produced from a five-stranded barrel with interspersed loop and helical components. They present significant structural divergence and so are with the capacity of binding a number of ligands furthermore to ssDNA and ssRNA (Theobald et al., 2003). Open up in another window Figure 1 Summary of ssDNA-Binding DomainsProteins are shaded tan, DNA is certainly shaded cyan, oxygen is certainly shaded crimson, nitrogen is shaded blue, and sulfur is certainly colored yellow. Parts of curiosity are highlighted in green. (A) OB-A from RPA70 (Proteins Data Lender [PDB] ID code 1JMC) binds ssDNA using aromatic and cation–stacking interactions, hydrophobic interactions, and base-mediated H bonds. Variable loop areas are proven in green. (B) KH1 from PCBP1 (PDB ID code 3VKE) binds ssDNA with an increase of phosphate-backbone contacts, but no intermolecular stacking interactions. The conserved GXXG motif is certainly proven in green. (C) RRM1 from hnRNP A1 (PDB ID code 2UP1) binds ssDNA utilizing a selection of interactions comparable to those observed in the OB folds and KH domains. Conserved RNP sequence motifs are proven in green. (D) Two of the four subunits of the Why2 complicated (PDB ID code 3N1J) are proven in tan and green. The user interface has many hydrophobic and stacking interactions, but minimal base-mediated H bonds. Known ssDNA ligands range long from 3 to 11 nt per OB fold and bind with dissociation constants that range between low-picomolar to high-micromolar amounts. Affinities approximately correlate with the distance of ssDNA bound and boost with the involvement of extra domains. DNA is certainly bound across a surface area of the Rabbit Polyclonal to EDG2 barrel generally devoted to strands 2 and 3 (Theobald et al., 2003). Loops augment the binding pocket, but may differ dramatically in proportions LEE011 reversible enzyme inhibition and participation in ligand reputation. The DNA typically binds with the bases toward the proteins and the backbone solvent uncovered and comes with an nearly universally conserved polarity over the binding surface area with the 5 end nearer to 3 and the 3 end nearer to 2 (Body 1A). The nucleotide LEE011 reversible enzyme inhibition bases take part in both intra- and intermolecular aromatic stacking in addition to cation- stacking. Hydrophobic and hydrogen-bonding interactions.

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