Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by its surface glycoprotein, Spike. The S1 subunit of Spike contains the N-terminal domain (NTD) and the receptor-binding domain (RBD), which mediates recognition of the host cell receptor angiotensinconverting enzyme 2 (ACE2). The S2 subunit drives fusion
Background: Orm proteins are key regulators of sphingolipid synthesis. Results: Orm1 and Orm2 are phosphorylated by TORC1 and TORC2; Orm2 is transcriptionally regulated by a calcium-and calcineurin-dependent pathway. Conclusion:The Orm proteins respond to feedback signals from the sphingolipid synthesis pathway and multiple environmental signals. Significance: Modulation of sphingolipid synthesis is a critical component of cellular response to nutritional status and stress.
We have constructed 26-amino acid transmembrane proteins that specifically transform cells but consist of only two different amino acids. Most proteins are long polymers of amino acids with 20 or more chemically distinct side-chains. The artificial transmembrane proteins reported here are the simplest known proteins with specific biological activity, consisting solely of an initiating methionine followed by specific sequences of leucines and isoleucines, two hydrophobic amino acids that differ only by the position of a methyl group. We designate these proteins containing leucine (L) and isoleucine (I) as LIL proteins. These proteins functionally interact with the transmembrane domain of the platelet-derived growth factor β-receptor and specifically activate the receptor to transform cells. Complete mutagenesis of these proteins identified individual amino acids required for activity, and a protein consisting solely of leucines, except for a single isoleucine at a particular position, transformed cells. These surprisingly simple proteins define the minimal chemical diversity sufficient to construct proteins with specific biological activity and change our view of what can constitute an active protein in a cellular context.T he chemical diversity of the 20 standard amino acid sidechains found in proteins supports myriad biochemical activities essential for life, and additional chemical diversity is generated by posttranslational amino acid modifications. The number of potential protein sequences is enormous: for proteins only 300 amino acids long, ∼10 400 possible sequences exist, a number larger by many orders-of-magnitude than the number of atoms in the known universe. This immense number of sequences and the chemical and conformational complexity of naturally occurring proteins hinder our ability to understand protein structure, folding, and function, and complicate protein engineering efforts. In addition, many different related amino acid sequences can fold into nearly identical structures, and even proteins with quite divergent sequences or protein folds can use similar chemistry to carry out related functions or display the same catalytic activity (e.g., refs. 1-3). These considerations further complicate attempts to clearly identify and understand the key structural features of proteins. Thus, the isolation of biologically active proteins with drastically reduced chemical complexity would represent a significant advance in protein science by facilitating the correlation of specific structural features with function.Up to 30% of all proteins contain ∼20-25-amino acid, primarily hydrophobic segments that span cell membranes (4). These transmembrane domains often play critical roles in cellular processes by engaging in highly specific protein-protein and protein-lipid interactions required for the proper folding, oligomerization, and function of transmembrane proteins (5-8). For example, receptor tyrosine kinases (RTKs) such as the PDGF-β receptor (PDGFβR) usually consist of an extracellular ligand binding do...
Summary The erythropoietin receptor (EPOR) plays an essential role in erythropoiesis and other cellular processes by forming distinct signaling complexes composed of EPOR homodimers or hetero-oligomers between the EPOR and another receptor, but the mechanism of heteroreceptor assembly and signaling is poorly understood. We report here a 46-residue, artificial transmembrane protein aptamer, designated ELI-3, that binds and activates the EPOR and induces growth factor independence in murine BaF3 cells expressing the EPOR. ELI-3 requires the transmembrane domain and JAK2-binding sites of the EPOR for activity, but not the cytoplasmic tyrosines that mediate canonical EPOR signaling. Instead, ELI-3-induced proliferation and activation of JAK/STAT signaling requires the transmembrane and cytoplasmic domains of the cytokine receptor β-common subunit (βcR) in addition to the EPOR. Moreover, ELI-3 fails to induce erythroid differentiation of primary human hematopoietic progenitor cells but inhibits nonhematopoietic cell death induced by serum withdrawal.
Authors are urged to introduce these corrections into any reprints they distribute. Secondary (abstract) services are urged to carry notice of these corrections as prominently as they carried the original abstracts.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.