Addition at the Molecular Level: Signal Integration in Designed Per–ARNT–Sim Receptor Proteins

Möglich, Andreas; Ayers, Rebecca A.; Moffat, Keith

doi:10.1016/j.jmb.2010.05.019

Cited by 70 publications

(94 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3). Five primary effector categories accounted for 83.1% of the LOV proteins in the sample set: protein kinase (serine/threonine kinase), F-box, Short LOVs (with terminal peptide extensions, similar to the fungal LOV domain VIVID) (7,(37)(38)(39), histidine kinase (HisKA), and PAS domains that may serve to integrate multiple environmental inputs with light (40). Nearly 1/10th of the sample set (7.2%) had no conserved domain matches in Pfam or Interpro despite extensions of 125-1,000+ residues that are much longer than those of short LOVs.…”

Section: Resultsmentioning

confidence: 99%

Functional and topological diversity of LOV domain photoreceptors

Glantz

Carpenter

Melkonian

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

132

155

View full text Add to dashboard Cite

Light-oxygen-voltage sensitive (LOV) flavoproteins are ubiquitous photoreceptors that mediate responses to environmental cues. Photosensory inputs are transduced into signaling outputs via structural rearrangements in sensor domains that consequently modulate the activity of an effector domain or multidomain clusters. Establishing the diversity in effector function and sensor-effector topology will inform what signaling mechanisms govern light-responsive behaviors across multiple kingdoms of life and how these signals are transduced. Here, we report the bioinformatics identification of over 6,700 candidate LOV domains (including over 4,000 previously unidentified sequences from plants and protists), and insights from their annotations for ontological function and structural arrangements. Motif analysis identified the sensors from ∼42 million ORFs, with strong statistical separation from other flavoproteins and non-LOV members of the structurally related Per-aryl hydrocarbon receptor nuclear translocator (ARNT)-Sim family. Conserved-domain analysis determined putative light-regulated function and multidomain topologies. We found that for certain effectors, sensor-effector linker length is discretized based on both phylogeny and the preservation of α-helical heptad repeats within an extended coiled-coil linker structure. This finding suggests that preserving sensor-effector orientation is a key determinant of linker length, in addition to ancestry, in LOV signaling structure-function. We found a surprisingly high prevalence of effectors with functions previously thought to be rare among LOV proteins, such as regulators of G protein signaling, and discovered several previously unidentified effectors, such as lipases. This work highlights the value of applying genomic and transcriptomic technologies to diverse organisms to capture the structural and functional variation in photosensory proteins that are vastly important in adaptation, photobiology, and optogenetics.photoreceptors | LOV | flavoproteins | optogenetics

show abstract

Section: Resultsmentioning

confidence: 99%

Functional and topological diversity of LOV domain photoreceptors

Glantz

Carpenter

Melkonian

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

132

155

View full text Add to dashboard Cite

show abstract

“…Due to their rigid structure, α helices and α-helical coiled coils are well-suited for transmitting conformational and dynamic changes over long distances between spatially distant sensors and effectors (Wolgemuth and Sun, 2006). Indeed, many natural signal receptors display sequence signatures indicative of helical and coiled-coil linkers (Anantharaman et al, 2006; Möglich et al, 2009a,b, 2010a; Rockwell et al, 2013). Furthermore, since α helices are self-contained structural elements stabilized by short-range contacts, locally confined order-disorder transitions, i.e., unfolding of helices, are enabled.…”

Section: Allostery Of Photoreceptorsmentioning

confidence: 99%

“…For several homodimeric photoreceptors, engineering is based on the exchange of light-inert chemosensors for structurally and functionally homologous LOV (Möglich et al, 2009a, 2010a) or bacteriophytochrome (Levskaya et al, 2005; Gasser et al, 2014; Ryu et al, 2014) photosensors. For example, we replaced the oxygen-sensitive PAS B domain of the histidine kinase FixL from Bradyrhizobium japonicum with the LOV domain of Bacillus subtilis YtvA to obtain the photoreceptor YF1.…”

Section: Allostery Of Photoreceptorsmentioning

confidence: 99%

Photoreceptor engineering

Ziegler

MÃ¶glich

2015

Front. Mol. Biosci.

115

148

View full text Add to dashboard Cite

Sensory photoreceptors not only control diverse adaptive responses in Nature, but as light-regulated actuators they also provide the foundation for optogenetics, the non-invasive and spatiotemporally precise manipulation of cellular events by light. Novel photoreceptors have been engineered that establish control by light over manifold biological processes previously inaccessible to optogenetic intervention. Recently, photoreceptor engineering has witnessed a rapid development, and light-regulated actuators for the perturbation of a plethora of cellular events are now available. Here, we review fundamental principles of photoreceptors and light-regulated allostery. Photoreceptors dichotomize into associating receptors that alter their oligomeric state as part of light-regulated allostery and non-associating receptors that do not. A survey of engineered photoreceptors pinpoints light-regulated association reactions and order-disorder transitions as particularly powerful and versatile design principles. Photochromic photoreceptors that are bidirectionally toggled by two light colors augur enhanced spatiotemporal resolution and use as photoactivatable fluorophores. By identifying desirable traits in engineered photoreceptors, we provide pointers for the design of future, light-regulated actuators.

show abstract

“…(2) Adapting the ability to rewire twocomponent pathways for synthetic biology efforts. Methods for rationally redirecting information flow within bacteria combined with advances in engineering histidine kinases with desired sensory capabilities [49][50][51] will enable the construction of sophisticated new signaling circuits.…”

Section: Discussionmentioning

confidence: 99%

Determinants of specificity in two-component signal transduction

Podgornaia

Laub

2013

Current Opinion in Microbiology

129

133

View full text Add to dashboard Cite

Maintaining the faithful flow of information through signal transduction pathways is critical to the survival and proliferation of organisms. This problem is particularly challenging as many signaling proteins are part of large, paralogous families that are highly similar at the sequence and structural levels, increasing the risk of unwanted cross-talk. To detect environmental signals and process information, bacteria rely heavily on two-component signaling systems comprised of sensor histidine kinases and their cognate response regulators. Although most species encode dozens of these signaling pathways, there is relatively little cross-talk, indicating that individual pathways are well insulated and highly specific. Here, we review the molecular mechanisms that enforce this specificity. Further, we highlight recent studies that have revealed how these mechanisms evolve to accommodate the introduction of new pathways by gene duplication.3

show abstract

Addition at the Molecular Level: Signal Integration in Designed Per–ARNT–Sim Receptor Proteins

Cited by 70 publications

References 45 publications

Functional and topological diversity of LOV domain photoreceptors

Functional and topological diversity of LOV domain photoreceptors

Photoreceptor engineering

Determinants of specificity in two-component signal transduction

Contact Info

Product

Resources

About