Insights into biological functions across species: examining the role of Rab proteins in YIP1 family function

2005 ◽  
Vol 33 (4) ◽  
pp. 614-618 ◽  
Author(s):  
C.Z. Chen ◽  
R.N. Collins
Keyword(s):  
Membrane Proteins ◽  
Protein Function ◽  
Evolutionary Conservation ◽  
Biological Role ◽  
Rab Proteins ◽  
Biological Functions ◽  
Human Homologue ◽  
Family Function ◽  
Evolutionarily Conserved

The YIP1 family comprises an evolutionarily conserved group of membrane proteins, which share the ability to bind di-prenylated Rab proteins. The biochemical capability of YIP1 family proteins suggests a possible role in the cycle of physical localization of Rab proteins between their cognate membranes and the cytosol. YIP1 is essential for viability in yeast and a deletion of YIP1 can be rescued with the human homologue YIP1A. We have made use of this evolutionary conservation of function to generate a series of mutant alleles of YIP1 to investigate the biological role of Yip1p. Our findings indicate evidence for the participation of Yip1p in both Rab and COPII protein function; at present, we are not able to distinguish between the models that these roles represent, i.e. independent or dependent activities of Yip1p.

scholarly journals SLC6A4 binding site and acute prosocial effects of (+/-)-3,4-methylendioxymethamphetamine (MDMA) are evolutionarily conserved in Octopus bimaculoides

2018 ◽  
Author(s):  
Eric Edsinger ◽  
Gül Dölen
Keyword(s):  
Binding Site ◽  
Social Behaviors ◽  
Evolutionary Conservation ◽  
Neural Mechanisms ◽  
Social Approach ◽  
Brain Organization ◽  
Invertebrate Species ◽  
Evolutionarily Conserved ◽  
Approach Behaviors

ABSTRACT:Human and octopus lineages are separated by over 500 million years of evolution, and show divergent anatomical patterns of brain organization. Moreover, while humans exhibit highly complex social behaviors, octopuses are thought to be largely asocial and solitary. Despite these differences, growing evidence suggests that ancient neurotransmitter systems are shared across vertebrate and invertebrate species, and in many cases enable overlapping functions. Here we provide evidence that, as in humans, the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) enhances acute prosocial behaviors in Octopus bimaculoides. This finding is paralleled by the evolutionary conservation of the serotonin transporter (SERT, encoded by the Slc6A4 gene) binding site of MDMA in the O. bimaculoides genome. Taken together, these data provide evidence that the neural mechanisms subserving social behaviors exist in O. bimaculoides, and indicate that the role of serotonergic neurotransmission in regulating social behaviors is evolutionarily conserved.ONE SENTENCE SUMMARY:Here we provide evidence that the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) increases acute social approach behaviors in Octopus bimaculoides, a finding that is paralleled by the evolutionary conservation of the SLC6A4 binding site of MDMA.

scholarly journals Assessing the Role of Lipids in the Molecular Mechanism of Membrane Proteins

2021 ◽  
Vol 22 (14) ◽  
pp. 7267
Author(s):  
Léni Jodaitis ◽  
Thomas van Oene ◽  
Chloé Martens
Keyword(s):  
Membrane Proteins ◽  
Molecular Mechanism ◽  
Protein Interactions ◽  
Protein Function ◽  
Biological Membrane ◽  
Allosteric Coupling ◽  
Lipid Protein Interactions ◽  
Experimental Challenge ◽  
Membrane Protein Function

Membrane proteins have evolved to work optimally within the complex environment of the biological membrane. Consequently, interactions with surrounding lipids are part of their molecular mechanism. Yet, the identification of lipid–protein interactions and the assessment of their molecular role is an experimental challenge. Recently, biophysical approaches have emerged that are compatible with the study of membrane proteins in an environment closer to the biological membrane. These novel approaches revealed specific mechanisms of regulation of membrane protein function. Lipids have been shown to play a role in oligomerization, conformational transitions or allosteric coupling. In this review, we summarize the recent biophysical approaches, or combination thereof, that allow to decipher the role of lipid–protein interactions in the mechanism of membrane proteins.

O-GlcNAc transferase inhibitors: current tools and future challenges

2016 ◽  
Vol 44 (1) ◽  
pp. 88-93 ◽  
Author(s):  
Riccardo Trapannone ◽  
Karim Rafie ◽  
Daan M.F. van Aalten
Keyword(s):  
Animal Models ◽  
Biological Systems ◽  
Biological Role ◽  
Present Review ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Embryonic Lethal ◽  
Future Challenges ◽  
Glcnac Transferase

The O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification (O-GlcNAcylation) is the dynamic and reversible attachment of N-acetylglucosamine to serine and threonine residues of nucleocytoplasmic target proteins. It is abundant in metazoa, involving hundreds of proteins linked to a plethora of biological functions with implications in human diseases. The process is catalysed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that add and remove sugar moieties respectively. OGT knockout is embryonic lethal in a range of animal models, hampering the study of the biological role of O-GlcNAc and the dissection of catalytic compared with non-catalytic roles of OGT. Therefore, selective and potent chemical tools are necessary to inhibit OGT activity in the context of biological systems. The present review focuses on the available OGT inhibitors and summarizes advantages, limitations and future challenges.

scholarly journals The Role of Phosphatidylethanolamine Adducts in Modification of the Activity of Membrane Proteins under Oxidative Stress

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4545 ◽  
Author(s):  
Elena E. Pohl ◽  
Olga Jovanovic
Keyword(s):  
Oxidative Stress ◽  
Membrane Proteins ◽  
Protein Function ◽  
Lipid Membrane ◽  
Membrane Lipids ◽  
Short Review ◽  
Membrane Properties ◽  
Complex Nature ◽  
Reactive Aldehydes

Reactive oxygen species (ROS) and their derivatives, reactive aldehydes (RAs), have been implicated in the pathogenesis of many diseases, including metabolic, cardiovascular, and inflammatory disease. Understanding how RAs can modify the function of membrane proteins is critical for the design of therapeutic approaches in the above-mentioned pathologies. Over the last few decades, direct interactions of RA with proteins have been extensively studied. Yet, few studies have been performed on the modifications of membrane lipids arising from the interaction of RAs with the lipid amino group that leads to the formation of adducts. It is even less well understood how various multiple adducts affect the properties of the lipid membrane and those of embedded membrane proteins. In this short review, we discuss a crucial role of phosphatidylethanolamine (PE) and PE-derived adducts as mediators of RA effects on membrane proteins. We propose potential PE-mediated mechanisms that explain the modulation of membrane properties and the functions of membrane transporters, channels, receptors, and enzymes. We aim to highlight this new area of research and to encourage a more nuanced investigation of the complex nature of the new lipid-mediated mechanism in the modification of membrane protein function under oxidative stress.

scholarly journals The architecture of the centriole cartwheel-containing region revealed by cryo-electron tomography

2020 ◽  
Author(s):  
Nikolai Klena ◽  
Maeva Le Guennec ◽  
Anne-Marie Tassin ◽  
Hugo van den Hoek ◽  
Philipp S. Erdmann ◽  
...  
Keyword(s):  
Electron Tomography ◽  
Evolutionary Conservation ◽  
Proximal Region ◽  
Single Bundle ◽  
The Core ◽  
Evolutionarily Conserved ◽  
Cryo Electron Tomography ◽  
Radial Spokes ◽  
Base Structure

AbstractCentrioles are evolutionarily conserved barrels of microtubule triplets that form the core of the centrosome and the base of the cilium. In the proximal region of the centriole, nine microtubule triplets attach to each other via A-C linkers and encircle a central cartwheel structure, which directs the early events of centriole assembly. While the crucial role of the proximal region in centriole biogenesis has been well documented in many species, its native architecture and evolutionary conservation remain relatively unexplored. Here, using cryo-electron tomography of centrioles from four evolutionarily distant species, including humans, we report on the architectural diversity of the centriolar proximal cartwheel-bearing region. Our work reveals that the cartwheel central hub, previously reported to have an 8.5 nm periodicity in Trichonympha, is constructed from a stack of paired rings with an average periodicity of ∼4 nm. In all four examined species, cartwheel inner densities are found inside the hub’s ring-pairs. In both Paramecium and Chlamydomonas, the repeating structural unit of the cartwheel has a periodicity of 25 nm and consists of three ring-pairs with 6 radial spokes emanating and merging into a single bundle that connects to the triplet microtubule via the pinhead. Finally, we identified that the cartwheel is indirectly connected to the A-C linker through a flexible triplet-base structure extending from the pinhead. Together, our work provides unprecedented evolutionary insights into the architecture of the centriole proximal region, which underlies centriole biogenesis.

scholarly journals An evolutionarily conserved enzyme degrades transforming growth factor-alpha as well as insulin.

1989 ◽  
Vol 109 (3) ◽  
pp. 1301-1307 ◽  
Author(s):  
J V Garcia ◽  
B D Gehm ◽  
M R Rosner
Keyword(s):  
Growth Factor ◽  
Mammalian Cells ◽  
Transforming Growth Factor ◽  
Physiological Role ◽  
Evolutionary Conservation ◽  
Transforming Growth Factor Alpha ◽  
Evolutionarily Conserved ◽  
Factor Alpha ◽  
Single Enzyme

A single enzyme found in both Drosophila and mammalian cells is able to selectively bind and degrade transforming growth factor (TGF)-alpha and insulin, but not EGF, at physiological concentrations. These growth factors are also able to inhibit binding and degradation of one another by the enzyme. Although there are significant immunological differences between the mammalian and Drosophila enzymes, the substrate specificity has been highly conserved. These results demonstrate the existence of a selective TGF-alpha-degrading enzyme in both Drosophila and mammalian cells. The evolutionary conservation of the ability to degrade both insulin and TGF-alpha suggests that this property is important for the physiological role of the enzyme and its potential for regulating growth factor levels.

scholarly journals A general mechanism for drug promiscuity: Studies with amiodarone and other antiarrhythmics

2015 ◽  
Vol 146 (6) ◽  
pp. 463-475 ◽  
Author(s):  
Radda Rusinova ◽  
Roger E. Koeppe ◽  
Olaf S. Andersen
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayer ◽  
Protein Function ◽  
Single Channel ◽  
General Mechanism ◽  
Antiarrhythmic Agents ◽  
Diverse Range ◽  
Lipid Mixtures ◽  
Membrane Protein Function

Amiodarone is a widely prescribed antiarrhythmic drug used to treat the most prevalent type of arrhythmia, atrial fibrillation (AF). At therapeutic concentrations, amiodarone alters the function of many diverse membrane proteins, which results in complex therapeutic and toxicity profiles. Other antiarrhythmics, such as dronedarone, similarly alter the function of multiple membrane proteins, suggesting that a multipronged mechanism may be beneficial for treating AF, but raising questions about how these antiarrhythmics regulate a diverse range of membrane proteins at similar concentrations. One possible mechanism is that these molecules regulate membrane protein function by altering the common environment provided by the host lipid bilayer. We took advantage of the gramicidin (gA) channels’ sensitivity to changes in bilayer properties to determine whether commonly used antiarrhythmics—amiodarone, dronedarone, propranolol, and pindolol, whose pharmacological modes of action range from multi-target to specific—perturb lipid bilayer properties at therapeutic concentrations. Using a gA-based fluorescence assay, we found that amiodarone and dronedarone are potent bilayer modifiers at therapeutic concentrations; propranolol alters bilayer properties only at supratherapeutic concentration, and pindolol has little effect. Using single-channel electrophysiology, we found that amiodarone and dronedarone, but not propranolol or pindolol, increase bilayer elasticity. The overlap between therapeutic and bilayer-altering concentrations, which is observed also using plasma membrane–like lipid mixtures, underscores the need to explore the role of the bilayer in therapeutic as well as toxic effects of antiarrhythmic agents.

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