keyword
MENU ▼
Read by QxMD icon Read
search

Unstructured Proteins

keyword
https://www.readbyqxmd.com/read/29049306/protein-structural-disorder-of-the-envelope-v3-loop-contributes-to-the-switch-in-human-immunodeficiency-virus-type-1-cell-tropism
#1
Xiaowei Jiang, Felix Feyertag, David L Robertson
Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically disordered (unstructured/disordered) protein as it contains regions that do not fold into well-defined protein structures. These disordered regions play important roles in HIV's life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections...
2017: PloS One
https://www.readbyqxmd.com/read/29046447/a-functional-carboxy-terminal-fluorescent-protein-fusion-to-pseudorabies-virus-small-capsid-protein-vp26
#2
Ian B Hogue, Jolie Jean, Andrew D Esteves, Nikhila S Tanneti, Julian Scherer, Lynn W Enquist
Fluorescent protein fusions to herpesvirus capsids have proven to be a valuable method to study virus particle transport in living cells. Fluorescent protein fusions to the amino terminus of small capsid protein VP26 are the most widely-used method to visualize Pseudorabies Virus (PRV) and Herpes Simplex Virus (HSV) particles in living cells. However, these fusion proteins do not incorporate to full occupancy, and have modest effects on virus replication and pathogenesis. Recent cryo electron microscopy studies have revealed that herpesvirus small capsid proteins bind to capsids via their amino terminus, whereas the carboxy terminus is unstructured and may therefore better tolerate fluorescent protein fusions...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29030482/membrane-scission-driven-by-the-proppin-atg18
#3
Navin Gopaldass, Bruno Fauvet, Hilal Lashuel, Aurélien Roux, Andreas Mayer
Sorting, transport, and autophagic degradation of proteins in endosomes and lysosomes, as well as the division of these organelles, depend on scission of membrane-bound tubulo-vesicular carriers. How scission occurs is poorly understood, but family proteins bind these membranes. Here, we show that the yeast PROPPIN Atg18 carries membrane scission activity. Purified Atg18 drives tubulation and scission of giant unilamellar vesicles. Upon membrane contact, Atg18 folds its unstructured CD loop into an amphipathic α-helix that inserts into the bilayer...
October 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29019235/the-impact-of-protonation-on-early-translocation-of-anthrax-lethal-factor-kinetics-from-molecular-dynamics-simulations-and-milestoning-theory
#4
Piao Ma, Alfredo E Cardenas, Mangesh I Chaudhari, Ron Elber, Susan B Rempe
We report atomically detailed molecular dynamics simulations of the permeation of the lethal factor (LF) N-terminal segment through the anthrax channel. The N-terminal chain is unstructured and leads the permeation process for the LF protein. The simulations were conducted in explicit solvent with milestoning theory, making it possible to extract kinetic information from nanosecond to millisecond time scales. We illustrate that the initial event is strongly influenced by the protonation states of the permeating amino acids...
October 12, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28992347/common-molecular-pathogenesis-of-disease-related-intrinsically-disordered-proteins-revealed-by-nmr-analysis
#5
Yoshiki Shigemitsu, Hidekazu Hiroaki
Intrinsically disordered proteins (IDPs) are either completely unstructured or contain large disordered regions in their native state; they have drawn much attention in the field of molecular pathology. Some of them substantially tend to form protein self-assemblies, such as toxic or non-toxic aggregates and fibrils, and have been postulated to relate to diseases. These disease-related IDPs include Aβ(1-42) [Alzheimer's disease (AD)], Tau (AD and tauopathy), α-synuclein (Parkinson's disease), and p53 (cancer)...
September 11, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28974728/addressing-the-role-of-the-%C3%AE-helical-extension-in-the-folding-of-the-third-pdz-domain-from-psd-95
#6
Candice Gautier, Lorenzo Visconti, Per Jemth, Stefano Gianni
PDZ domains are one of the most important protein-protein interaction domains in human. While presenting a conserved three dimensional structure, a substantial number of PDZ domains display structural extensions suggested to be involved in their folding and binding mechanisms. The C-terminal α-helix extension (α3) of the third PDZ domain from PSD-95 (PDZ3) has been reported to have a role in function of the domain as well as in the stabilization of the native fold. Here we report an evaluation of the effect of the truncation of this additional helix on the folding and unfolding kinetics of PDZ3...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28960199/preserving-protein-function-through-reversible-aggregation
#7
Jörg Höhfeld
It is generally accepted that protein function depends on a defined 3D structure, with unfolding and aggregation dealing a final blow to functionality. A study now shows that the regulated exposure of an unstructured region in yeast pyruvate kinase triggers reversible aggregation to preserve protein function under stress.
September 29, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28924049/specific-electrostatic-interactions-between-charged-amino-acid-residues-regulate-binding-of-von-willebrand-factor-to-blood-platelets
#8
Gianluca Interlandi, Olga Yakovenko, An-Yue Tu, Jeff Harris, Jennie Le, Junmei Chen, José A López, Wendy E Thomas
The plasma protein von Willebrand factor (VWF) is essential for hemostasis initiation at sites of vascular injury. The platelet binding A1 domain of VWF is connected to the VWF's N-terminally located D'D3 domain through a relatively unstructured amino acid sequence, called here the N-terminal linker. This region has previously been shown to inhibit the binding of VWF to the platelet surface receptor glycoprotein Ibα (GpIbα). However, the molecular mechanism underlying the inhibitory function of the N-terminal linker has not been elucidated...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28894085/p190rhogap-proteins-contain-pseudogtpase-domains
#9
Amy L Stiegler, Titus J Boggon
The two p190RhoGAP proteins, p190RhoGAP-A and -B, are key regulators of Rho GTPase signaling and are essential for actin cytoskeletal structure and contractility. Here we report the discovery of two evolutionarily conserved GTPase-like domains located in the 'middle domain', previously thought to be unstructured. Deletion of these domains reduces RhoGAP activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays and sequence homology analysis all strongly support defects in nucleotide-binding activity...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28893902/the-cytosolic-domain-of-t-cell-receptor-%C3%AE-associates-with-membranes-in-a-dynamic-equilibrium-and-deeply-penetrates-the-bilayer
#10
Kerstin Zimmermann, Rebecca Eells, Frank Heinrich, Stefanie Rintoul, Brian Josey, Prabhanshu Shekhar, Mathias Lösche, Lawrence J Stern
Interactions between lipid bilayers and the membrane-proximal regions of membrane-associated proteins play important roles in regulat-ing membrane protein structure and function. The T-cell antigen receptor (TCR) is an assembly of eight single-pass membrane-spanning subunits on the surface of T-lymphocytes that initiates cytosolic signaling cascades upon binding antigens presented by MHC-family proteins on antigen-presenting cells. Its ζ subunit contains multiple cytosolic immunoreceptor tyrosine-based activation motifs (ITAMs) involved in signal transduction, and this subunit by itself is sufficient to couple extracellular stimuli to intracellular signaling events...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28880689/prodromal-signs-and-symptoms-of-serious-infections-with-tocilizumab-treatment-for-rheumatoid-arthritis-text-mining-of-the-japanese-postmarketing-adverse-event-reporting-database
#11
Tatsuya Atsumi, Yoshiaki Ando, Shinichi Matsuda, Shiho Tomizawa, Riwa Tanaka, Nobuhiro Takagi, Ayako Nakasone
OBJECTIVE: To search for signs and symptoms before serious infection (SI) occurs in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients. METHODS: Individual case safety reports, including structured (age, sex, adverse event [AE]) and unstructured (clinical narratives) data, were analyzed by automated text mining from a Japanese post-marketing AE-reporting database (16 April 2008-10 April 2015) assuming the following: treated in Japan; TCZ RA treatment; ≥1 SI; unable to exclude causality between TCZ and SIs...
September 7, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28877466/local-nucleation-of-microtubule-bundles-through-tubulin-concentration-into-a-condensed-tau-phase
#12
Amayra Hernández-Vega, Marcus Braun, Lara Scharrel, Marcus Jahnel, Susanne Wegmann, Bradley T Hyman, Simon Alberti, Stefan Diez, Anthony A Hyman
Non-centrosomal microtubule bundles play important roles in cellular organization and function. Although many diverse proteins are known that can bundle microtubules, biochemical mechanisms by which cells could locally control the nucleation and formation of microtubule bundles are understudied. Here, we demonstrate that the concentration of tubulin into a condensed, liquid-like compartment composed of the unstructured neuronal protein tau is sufficient to nucleate microtubule bundles. We show that, under conditions of macro-molecular crowding, tau forms liquid-like drops...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28870607/circular-dichroism-in-functional-quality-evaluation-of-medicines
#13
REVIEW
Han Yao, Evelien Wynendaele, Xiaolong Xu, Anne Kosgei, Bart De Spiegeleer
Circular dichroism (CD) is a non-destructive and powerful technique for providing structure and ligand interaction information of small molecules as well as biotechnological medicines. While CD is a well-established technique in biomedical research, and different types and variants of CD do exist, the focus of this review is on the pharmaceutical quality control (QC) aspects of the classic electronic CD (ECD). The basic principles of the CD technique are initially described, followed by a systematic literature research on pharmaceutical aspects encompassing chiral small molecules, bio-polymers (i...
August 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28864230/there-is-an-inclusion-for-that-material-properties-of-protein-granules-provide-a-platform-for-building-diverse-cellular-functions
#14
REVIEW
Daniel Kaganovich
Proteins perform a staggering variety of functions in the cell. Traditionally, protein function was thought to be hard-wired into the folded structure and conformational dynamics of each protein molecule. Recent work describes a new mode of protein functionality driven by the collective behavior of many different proteins; most of which lack a defined structure. These proteins form clusters or granules in which unstructured polypeptides interact transiently. Nonspecific multivalent interactions drive the formation of phase-separated structures resembling aggregates...
October 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28857311/engineered-highly-reactive-substrates-of-microbial-transglutaminase-enable-protein-labeling-within-various-secondary-structure-elements
#15
Natalie M Rachel, Daniela Quaglia, Éric Lévesque, André B Charette, Joelle N Pelletier
Microbial transglutaminase (MTG) is a practical tool to enzymatically form isopeptide bonds between peptide or protein substrates. This natural approach to crosslinking the side-chains of reactive glutamine and lysine residues is solidly rooted in food and textile processing. More recently, MTG's tolerance for various primary amines in lieu of lysine have revealed its potential for site-specific protein labeling with aminated compounds, including fluorophores. Importantly, MTG can label glutamines at accessible positions in the body of a target protein, setting it apart from most labeling enzymes that react exclusively at protein termini...
August 31, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28838668/copper-and-zinc-promoted-interdomain-structure-in-the-prion-protein-a-mechanism-for-autoinhibition-of-the-neurotoxic-n-terminus
#16
Eric G B Evans, Glenn L Millhauser
The function of the cellular prion protein (PrP(C)), while still poorly understood, is increasingly linked to its ability to bind physiological metal ions at the cell surface. PrP(C) binds divalent forms of both copper and zinc through its unstructured N-terminal domain, modulating interactions between PrP(C) and various receptors at the cell surface and ultimately tuning downstream cellular processes. In this chapter, we briefly discuss the molecular features of copper and zinc uptake by PrP(C) and summarize evidence implicating these metal ions in PrP-mediated physiology...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28835493/prp-p102l-and-nearby-lysine-mutations-promote-spontaneous-in-vitro-formation-of-transmissible-prions
#17
Allison Kraus, Gregory J Raymond, Brent Race, Katrina J Campbell, Andrew G Hughson, Kelsie J Anson, Lynne D Raymond, Byron Caughey
Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro, only some are transmissible and pathogenic in vivo To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28833749/amyloidogenesis-of-tau-protein
#18
REVIEW
Bartosz Nizynski, Wojciech Dzwolak, Krzysztof Nieznanski
The role of microtubule-associated protein Tau in neurodegeneration has been extensively investigated since the discovery of Tau amyloid aggregates in the brains of patients with Alzheimer's disease (AD). The process of formation of amyloid fibrils is known as amyloidogenesis and attracts much attention as a potential target in the prevention and treatment of neurodegenerative conditions linked to protein aggregation. Cerebral deposition of amyloid aggregates of Tau is observed not only in AD but also in numerous other tauopathies and prion diseases...
August 17, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28821615/distinct-structural-mechanisms-determine-substrate-affinity-and-kinase-activity-of-protein-kinase-c%C3%AE
#19
Sangbae Lee, Titu Devamani, Hyun Deok Song, Manbir Sandhu, Adrien Larsen, Ruth Sommese, Abhinandan Jain, Nagarajan Vaidehi, Sivaraj Sivaramakrishnan
Protein kinase Cα (PKCα) belongs to the family of AGC kinases that phosphorylate multiple peptide substrates. Although the consensus sequence motif has been identified and used to explain substrate specificity for PKCα, it does not inform the structural basis of substrate-binding and kinase activity for diverse substrates phosphorylated by this kinase. The transient, dynamic, and unstructured nature of this protein-protein interaction has limited structural mapping of kinase-substrate interfaces. Here, using multiscale MD simulation-based predictions and FRET sensor-based experiments, we investigated the conformational dynamics of the kinase-substrate interface...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28808112/regulation-of-perforin-activation-and-pre-synaptic-toxicity-through-c-terminal-glycosylation
#20
Imran G House, Colin M House, Amelia J Brennan, Omer Gilan, Mark A Dawson, James C Whisstock, Ruby Hp Law, Joseph A Trapani, Ilia Voskoboinik
Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. Prior to delivery to target cells by exocytosis, perforin is stored in acidic secretory granules where it remains functionally inert. However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca(2+)-rich endoplasmic reticulum, remains unknown. Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation...
October 2017: EMBO Reports
keyword
keyword
13280
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"