The Light-Oxygen-Voltage domain family of proteins is widespread in biology where they impart sensory responses to signal transduction domains. The small, light responsive LOV modules offer a novel platform for the construction of optogenetic tools. Currently, the design and implementation of these devices is partially hindered by a lack of understanding of how light drives allosteric changes in protein conformation to activate diverse signal transduction domains. Further, divergent photocycle properties amongst LOV family members complicate construction of highly sensitive devices with fast on/off kinetics. In the present review we discuss the history of LOV domain research with primary emphasis on tuning LOV domain chemistry and signal transduction to allow for improved optogenetic tools.

Light Oxygen Voltage (LOV) proteins are widely used in optogenetic devices, however universal signal transduction pathways and photocycle mechanisms remain elusive. In particular, short-LOV (sLOV) proteins have been discovered in bacteria and fungi, containing only the photoresponsive LOV element without any obvious signal transduction domains. These sLOV proteins may be ideal models for LOV domain function due to their ease of study as full-length proteins. Unfortunately, characterization of such proteins remains limited to select systems. Herein, we identify a family of bacterial sLOV proteins present in Methylocystis. Sequence analysis of Methylocystis LOV proteins (McLOV) demonstrates conservation with sLOV proteins from fungal systems that employ competitive dimerization as a signaling mechanism. Cloning and characterization of McLOV proteins confirms functional dimer formation and reveal unexpected photocycle mechanisms. Specifically, some McLOV photocycles are insensitive to external bases such as imidazole, in contrast to previously characterized LOV proteins. Mutational analysis identifies a key residue that imparts insensitivity to imidazole in two McLOV homologs and affects adduct decay by two orders of magnitude. The resultant data identifies a new family of LOV proteins that indicate a universal photocycle mechanism may not be present in LOV proteins.

Langerhans cell histiocytosis (LCH) is a rare disorder defined by the abnormal proliferation of Langerhans cells. While LCH can present at any age, it is classically described as a pediatric condition, and is therefore overlooked in the adult patient. Additionally, depending on tumor burden and location, LCH can manifest with a host of oral and systemic symptoms which further confuses the clinical presentation and ultimate diagnosis. The authors present a unique report of an elderly Hispanic male diagnosed with mandibular LCH who sought primary tumor excision after neoadjuvant chemotherapy. In this study, a fibula-free flap was used for subsequent reconstruction. The purpose of the study is 2-fold: to highlight the variability of LCH in both patient symptomatology and demographics, as well as the role of plastic reconstructive surgery in definitive LCH management, particularly in the setting of single system unifocal disease.