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The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity

In this hybrid review, we have first collected and reviewed available information on the structure and function of the enigmatic cache domains in α2δ proteins. These are organized into two double cache (dCache_1) domains, and they are present in all …

Photoactive Yellow Protein Represents a Distinct, Evolutionarily Novel Family of PAS Domains

Photoactive yellow protein (PYP) is a model photoreceptor. It binds a p-coumaric acid as a chromophore, thus enabling blue light sensing. The first discovered single-domain PYP from Halorhodospira halophila has been studied thoroughly in terms of its …

Phyletic Distribution and Diversification of the Phage Shock Protein Stress Response System in Bacteria and Archaea

Maintaining cell envelope integrity is of vital importance for all microorganisms. Not surprisingly, evolution has shaped conserved protein protection networks that connect stress perception, transmembrane signal transduction, and mediation of …

Biallelic CACNA2D1 loss-of-function variants cause early-onset developmental epileptic encephalopathy

Voltage-gated calcium (CaV) channels form three sub-families (CaV1-3). The CaV1 and CaV2 channels are heteromeric, consisting of an α1 pore-forming subunit, associated with auxiliary CaVβ and α2δ subunits. The α2δ subunits are encoded in mammals by …

Amino acid sensor conserved from bacteria to humans

Amino acids are the building blocks of life, and they are also recognized as signals by various receptors in bacteria, archaea, and eukaryotes. Despite their common basic structure, no universal mechanism for amino acid recognition is currently …

A species-specific functional module controls formation of pollen apertures

Pollen apertures are an interesting model for the formation of specialized plasma-membrane domains. The plant-specific protein INP1 serves as a key aperture factor in such distantly related species as Arabidopsis, rice and maize. Although INP1 …

Diversity of bacterial chemosensory systems

Chemosensory system is the most complex, specialized mode of signal transduction in bacteria and archaea. It is composed of several core and auxiliary protein components that are highly organized in order to deliver a fast response to changing …

The Campylobacter jejuni chemoreceptor Tlp10 has a bimodal ligand-binding domain and specificity for multiple classes of chemoeffectors

Campylobacter jejuni is a bacterial pathogen that is a common cause of enteritis in humans. We identified a previously uncharacterized type of sensory domain in the periplasmic region of the C. jejuni chemoreceptor Tlp10, termed the DAHL domain, that …

Origins and Molecular Evolution of the NusG Paralog RfaH

IMPORTANCE In all domains of life, NusG-like proteins make contacts similar to those of RNA polymerase and promote pause-free transcription yet may play different roles, defined by their divergent interactions with nucleic acids and accessory proteins, in the same cell. This duality is illustrated by Escherichia coli NusG and RfaH, which silence and activate xenogenes, respectively. We combined sequence analysis and recent functional and structural insights to envision the evolutionary transformation of NusG, a core regulator that we show is present in all cells using bacterial RNA polymerase, into a virulence factor, RfaH. Our results suggest a stepwise conversion of a NusG duplicate copy into a sequence-specific regulator which excludes NusG from its targets but does not compromise the regulation of housekeeping genes. We find that gene duplication and lateral transfer give rise to a surprising diversity within the only ubiquitous family of transcription factors.

Identification and characterization of a novel CLCN7 variant associated with osteopetrosis

Osteopetrosis is a group of rare inheritable disorders of the skeleton characterized by increased bone density. The disease is remarkably heterogeneous in clinical presentation and often misdiagnosed. Therefore, genetic testing and molecular …