scholarly journals Structural Diversity in Conserved Regions Like the DRY-Motif among Viral 7TM Receptors—A Consequence of Evolutionary Pressure?

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Ann-Sofie Mølleskov Jensen ◽  
Alexander Hovard Sparre-Ulrich ◽  
Nicholas Davis-Poynter ◽  
Mette Marie Rosenkilde
Keyword(s):  
Chemokine Receptors ◽  
Regulatory Region ◽  
Structural Diversity ◽  
Phosphorylation Sites ◽  
Human Class ◽  
Structural Motifs ◽  
Class A ◽  
Dry Motif ◽  
Viral Receptors ◽  
7Tm Receptors

Several herpes- and poxviruses have captured chemokine receptors from their hosts and modified these to their own benefit. The human and viral chemokine receptors belong to class A 7 transmembrane (TM) receptors which are characterized by several structural motifs like the DRY-motif in TM3 and the C-terminal tail. In the DRY-motif, the arginine residue serves important purposes by being directly involved in G protein coupling. Interestingly, among the viral receptors there is a greater diversity in the DRY-motif compared to their endogenous receptor homologous. The C-terminal receptor tail constitutes another regulatory region that through a number of phosphorylation sites is involved in signaling, desensitization, and internalization. Also this region is more variable among virus-encoded 7TM receptors compared to human class A receptors. In this review we will focus on these two structural motifs and discuss their role in viral 7TM receptor signaling compared to their endogenous counterparts.

Production, characterization, and interspecies reactivities of monoclonal antibodies against human class A macrophage scavenger receptors

2002 ◽  
Vol 161 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Ryu-ichiro Tomokiyo ◽  
Katsunori Jinnouchi ◽  
Makoto Honda ◽  
Youichiro Wada ◽  
Norihisa Hanada ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Scavenger Receptors ◽  
Human Class ◽  
Class A

Thioborates: potential nonlinear optical materials with rich structural chemistry

2017 ◽  
Vol 46 (13) ◽  
pp. 4134-4147 ◽  
Author(s):  
Yu-kun Lian ◽  
Li-Ming Wu ◽  
Ling Chen
Keyword(s):  
Optical Materials ◽  
Nonlinear Optical ◽  
Damage Threshold ◽  
Structural Diversity ◽  
Optical Nonlinearity ◽  
Structural Chemistry ◽  
Nonlinear Optical Materials ◽  
Three Dimension ◽  
Structural Motifs ◽  
Laser Induced Damage

This review summarizes thioborates and their structural motifs ranging from zero-dimension to three-dimension. The most commonly observed building units of these examples are planar-triangle BS3 and tetrahedron BS4. Thioborates possess advantages with respect to their structural diversity, optical nonlinearity, laser-induced damage threshold and transparency range, and represent potentially a rich supply of new nonlinear optical materials.

scholarly journals The Nef Protein of Human Immunodeficiency Virus Is a Broad-Spectrum Modulator of Chemokine Receptor Cell Surface Levels That Acts Independently of Classical Motifs for Receptor Endocytosis and GαiSignaling

2006 ◽  
Vol 17 (8) ◽  
pp. 3578-3590 ◽  
Author(s):  
Nico Michel ◽  
Kerstin Ganter ◽  
Stephanie Venzke ◽  
Julia Bitzegeio ◽  
Oliver T. Fackler ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Chemokine Receptors ◽  
Inflammatory Responses ◽  
Viral Disease ◽  
Immune Defense ◽  
Heterotrimeric G Proteins ◽  
Receptor Endocytosis ◽  
Immunodeficiency Virus ◽  
Dry Motif

Chemokine receptors (CKRs) are important physiological mediators of immune defense, inflammatory responses, and angiogenesis, and they have also been implicated in a number of viral disease processes. Here, we report that the Nef protein of human immunodeficiency virus (HIV) reduces cell surface levels of eight different members of the CC- and CXC-family of CKRs by up to 92%. This broad-range activity required specific elements in HIVSF2Nef, including the proline-rich motif P73P76P79P82as well as the acidic cluster motif E66E67E68E69, and Nef expression induced a marked perinuclear accumulation of CKRs. Surprisingly, receptor mutagenesis demonstrated that the cytoplasmic tail of CCR5 and CXCR4, which is critical for basal and ligand-mediated endocytosis, was completely dispensable for this Nef activity. In contrast, triple-mutation of the highly conserved DRY motif in the second intracellular CKR loop abolished the Nef-mediated down-regulation of CXCR4 independently of this motif’s role in CKR binding to heterotrimeric G proteins and signaling via the Gαisubunit. Thus, we identify the lentiviral pathogenicity factor Nef as a unique and broad-range modulator of CKR cell surface levels. Nef uses a mechanism that is distinct from well-established pathways orchestrating CKR metabolism and offers an interesting tool to study the multifaceted biology of CKRs.

scholarly journals Structural diversity of human class II histocompatibility molecules induced by peptide ligands

FEBS Letters ◽  
2000 ◽  
Vol 481 (3) ◽  
pp. 249-254 ◽  
Author(s):  
Bertrand Georges ◽  
Estelle Loing ◽  
Raphaële Neveu ◽  
Oleg Melnyk ◽  
Helene Gras-Masse ◽  
...  
Keyword(s):  
Structural Diversity ◽  
Class Ii ◽  
Peptide Ligands ◽  
Human Class

scholarly journals Alternative AKT2 splicing produces protein lacking the hydrophobic motif regulatory region

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242819
Author(s):  
Guido Plotz ◽  
Laura A. Lopez-Garcia ◽  
Angela Brieger ◽  
Stefan Zeuzem ◽  
Ricardo M. Biondi
Keyword(s):  
Splice Variant ◽  
Specific Activity ◽  
Regulatory Region ◽  
Pi3 Kinase ◽  
Hek293 Cells ◽  
Phosphorylation Sites ◽  
Catalytic Core ◽  
Agc Kinases ◽  
Akt Isoforms ◽  
Hydrophobic Motif

Three AKT serine/threonine kinase isoforms (AKT1/AKT2/AKT3) mediate proliferation, metabolism, differentiation and anti-apoptotic signals. AKT isoforms are activated downstream of PI3-kinase and also by PI3-kinase independent mechanisms. Mutations in the lipid phosphatase PTEN and PI3-kinase that increase PIP3 levels increase AKT signaling in a large proportion of human cancers. AKT and other AGC kinases possess a regulatory mechanism that relies on a conserved hydrophobic motif (HM) C-terminal to the catalytic core. In AKT, the HM is contiguous to the serine 473 and two other newly discovered (serine 477 and tyrosine 479) regulatory phosphorylation sites. In AKT genes, this regulatory HM region is encoded in the final exon. We identified a splice variant of AKT2 (AKT2-13a), which contains an alternative final exon and lacks the HM regulatory site. We validated the presence of mRNA for this AKT2-13a splice variant in different tissues, and the presence of AKT2-13a protein in extracts from HEK293 cells. When overexpressed in HEK293 cells, AKT2-13a is phosphorylated at the activation loop and at the zipper/turn motif phosphorylation sites but has reduced specific activity. Analysis of the human transcriptome corresponding to other AGC kinases revealed that all three AKT isoforms express alternative transcripts lacking the HM regulatory motif, which was not the case for SGK1-3, S6K1-2, and classical, novel and atypical PKC isoforms. The transcripts of splice variants of Akt1-3 excluding the HM regulatory region could lead to expression of deregulated forms of AKT.

scholarly journals In Silico Identification of Cholesterol Binding Motifs in the Chemokine Receptor CCR3

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 570
Author(s):  
Evan van van Aalst ◽  
Jotham Koneri ◽  
Benjamin J. Wylie
Keyword(s):  
Chemokine Receptor ◽  
Binding Sites ◽  
In Silico ◽  
Chemokine Receptors ◽  
Homology Model ◽  
Binding Pocket ◽  
Coarse Grained ◽  
Class A ◽  
Inflammatory Conditions ◽  
Cholesterol Binding

CC motif chemokine receptor 3 (CCR3) is a Class A G protein-coupled receptor (GPCR) mainly responsible for the cellular trafficking of eosinophils. As such, it plays key roles in inflammatory conditions, such as asthma and arthritis, and the metastasis of many deadly forms of cancer. However, little is known about how CCR3 functionally interacts with its bilayer environment. Here, we investigate cholesterol binding sites in silico through Coarse-Grained Molecular Dynamics (MD) and Pylipid analysis using an extensively validated homology model based on the crystal structure of CCR5. These simulations identified several cholesterol binding sites containing Cholesterol Recognition/Interaction Amino Acid Consensus motif (CRAC) and its inversion CARC motifs in CCR3. One such site, a CARC site in TM1, in conjunction with aliphatic residues in TM7, emerged as a candidate for future investigation based on the cholesterol residency time within the binding pocket. This site forms the core of a cholesterol binding site previously observed in computational studies of CCR2 and CCR5. Most importantly, these cholesterol binding sites are conserved in other chemokine receptors and may provide clues to cholesterol regulation mechanisms in this subfamily of Class A GPCRs.

The Highly Conserved DRY Motif of Class A G Protein-Coupled Receptors: Beyond the Ground State

2006 ◽  
Vol 71 (4) ◽  
pp. 959-964 ◽  
Author(s):  
G. Enrico Rovati ◽  
Valérie Capra ◽  
Richard R. Neubig
Keyword(s):  
G Protein ◽  
Ground State ◽  
G Protein Coupled Receptors ◽  
Class A ◽  
Dry Motif ◽  
G Protein Coupled

scholarly journals The 3' regulatory region of the Abdominal-B gene: genetic analysis supports a model of reiterated and interchangeable regulatory elements.

Genetics ◽  
1993 ◽  
Vol 134 (3) ◽  
pp. 809-824
Author(s):  
M A Crosby ◽  
E A Lundquist ◽  
R M Tautvydas ◽  
J J Johnson
Keyword(s):  
Regulatory Region ◽  
Regulatory Elements ◽  
Molecular Techniques ◽  
Regulatory Sequences ◽  
Homeotic Genes ◽  
Class A ◽  
Adjacent Position ◽  
Cell Type Specific ◽  
Position Sensitive

Abstract The Abdominal-B (Abd-B) gene is one of three genes in the bithorax complex, a cluster of homeotic genes in Drosophila. During embryogenesis Abd-B is expressed in a complex pattern, producing four different transcript classes, each of which exhibits a unique spatial pattern of expression. Proper regulation of the class A transcripts is required for appropriate development of the fifth through eighth abdominal segments and is mediated, in part, by a 60-kb regulatory region located 3' of the gene. We have isolated a new mutation, designated Abd-BCorset, which is caused by a deletion that leaves 15 kb of the 3' regulatory sequences immediately adjacent to the gene, but removes 45 kb of the more distant 3' regulatory elements. This mutation produces an unexpected homeotic segmental transformation of the fourth through seventh abdominal segments, and has been analyzed by genetic and molecular techniques. In situ hybridization to Abd-BCorset embryos shows a uniform and moderate level of the Abd-B class A transcript in the posterior abdomen, rather than the normal graded pattern of expression. Our analysis of the Abd-BCorset mutation has prompted a model of the 3' regulatory region of Abd-B based on reiterated cell type-specific elements controlled by adjacent position-sensitive activating elements. The gradient of Abd-B expression normally observed in the posterior abdomen appears to be achieved by varying the number of reiterated elements that are active in each segment.

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