Fatty-acylation target sequence in the ligand-binding domain of vertebrate steroid receptors demarcates evolution from estrogen-related receptors

The Journal of Steroid Biochemistry and Molecular Biology
Richard Lathe, Douglas R Houston

Abstract

Present-day nuclear receptors (NRs) responding to adrenal and sex steroids are key regulators of reproduction and growth in mammals, and are thought to have evolved from an ancestral NR most closely related to extant estrogen-related receptors (ERRs). The molecular events (and ligands) that distinguish steroid-activated NRs (SRs) from their inferred ancestor, that gave rise to both the ERRs and SRs, remain unknown. We report that target sequences for fatty-acylation (palmitoylation) at a key cysteine residue (corresponding to Cys447 in human estrogen receptor ERα) in helix 8 of the ligand-binding domain accurately demarcate SRs from ERRs. Docking studies are consistent with the hypothesis that palmitate embeds into a key groove in the receptor surface. The implications of lipidation, and of potential alternative ligands for the key cysteine residue, for receptor function and the evolution of SRs are discussed.

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.