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Structural variation affecting DNA backbone interactions underlies adaptation of B3 DNA binding domains to constraints imposed by protein architecture.

ABSTRACT: Functional and architectural diversification of transcription factor families has played a central role in the independent evolution of complex development in plants and animals. Here, we investigate the role of architectural constraints on evolution of B3 DNA binding domains that regulate plant embryogenesis. B3 domains of ABI3, FUS3, LEC2 and VAL1 proteins recognize the same cis-element. Complex architectures of ABI3 and VAL1 integrate cis-element recognition with other signals, whereas LEC2 and FUS3 have reduced architectures conducive to roles as pioneer activators. In yeast and plant in vivo assays, B3 domain functions correlate with architectural complexity of the parent transcription factor rather than phylogenetic relatedness. In a complex architecture, attenuated ABI3-B3 and VAL1-B3 activities enable integration of cis-element recognition with hormone signaling, whereas hyper-active LEC2-B3 and FUS3-B3 over-ride hormonal control. Three clade-specific amino acid substitutions (β4-triad) implicated in interactions with the DNA backbone account for divergence of LEC2-B3 and ABI3-B3. We find a striking correlation between differences in in vitro DNA binding affinity and in vivo activities of B3 domains in plants and yeast. Our results highlight the role of DNA backbone interactions that preserve DNA sequence specificity in adaptation of B3 domains to functional constraints associated with domain architecture.

SUBMITTER: Jia H

PROVIDER: S-EPMC8136769 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Ring-shaped sliding clamps encircle DNA and bind to DNA polymerase, thereby preventing it from falling off during DNA replication. In eukaryotes, sliding clamps are loaded onto DNA by the replication factor C (RFC) complex, which consists of five distinct subunits (A-E), each of which contains an AAA+ module composed of a RecA-like alpha/beta ATPase domain followed by a helical domain. AAA+ ATPases mediate chaperone-like protein remodeling. Despite remarkable progress in our understanding of clamp loaders, it is still unclear how recognition of primed DNA by RFC triggers ATP hydrolysis and how hydrolysis leads to conformational changes that can load the clamp onto DNA. While these questions can, of course, only be resolved experimentally, the design of such experiments is itself non-trivial and requires that one first formulate the right hypotheses based on preliminary observations. The functional constraints imposed on protein sequences during evolution are potential sources of information in this regard, inasmuch as these presumably are due to and thus reflect underlying mechanisms. Here, rigorous statistical procedures are used to measure and compare the constraints imposed on various RFC clamp-loader subunits, each of which performs a related but somewhat different, specialized function. Visualization of these constraints, within the context of the RFC structure, provides clues regarding clamp-loader mechanisms--suggesting, for example, that RFC-A possesses a triggering component for DNA-dependent ATP hydrolysis. It also suggests that, starting with RFC-A, four RFC subunits (A-D) are sequentially activated through a propagated switching mechanism in which a conserved arginine swings away from a position that disrupts the catalytic Walker B region and into contact with DNA thread through the center of the RFC/clamp complex. Strong constraints near regions of interaction between subunits and with the clamp likewise provide clues regarding possible coupling of hydrolysis-driven conformational changes to the clamp's release and loading onto DNA.

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Structural variation affecting DNA backbone interactions underlies adaptation of B3 DNA binding domains to constraints imposed by protein architecture.

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