keyword
MENU ▼
Read by QxMD icon Read
search

Protein unfolding and translocation

keyword
https://www.readbyqxmd.com/read/28815021/toward-an-understanding-of-the-cdc48-p97-atpase
#1
REVIEW
Nicholas Bodnar, Tom Rapoport
A conserved AAA+ ATPase, called Cdc48 in yeast and p97 or VCP in metazoans, plays an essential role in many cellular processes by segregating polyubiquitinated proteins from complexes or membranes. For example, in endoplasmic reticulum (ER)-associated protein degradation (ERAD), Cdc48/p97 pulls polyubiquitinated, misfolded proteins out of the ER and transfers them to the proteasome. Cdc48/p97 consists of an N-terminal domain and two ATPase domains (D1 and D2). Six Cdc48 monomers form a double-ring structure surrounding a central pore...
2017: F1000Research
https://www.readbyqxmd.com/read/28811582/a-new-class-of-hybrid-secretion-system-is-employed-in-pseudomonas-amyloid-biogenesis
#2
Sarah L Rouse, William J Hawthorne, Jamie-Lee Berry, Dror S Chorev, Sandra A Ionescu, Sebastian Lambert, Fisentzos Stylianou, Wiebke Ewert, Uma Mackie, R Marc L Morgan, Daniel Otzen, Florian-Alexander Herbst, Per H Nielsen, Morten Dueholm, Hagan Bayley, Carol V Robinson, Stephen Hare, Stephen Matthews
Gram-negative bacteria possess specialised biogenesis machineries that facilitate the export of amyloid subunits for construction of a biofilm matrix. The secretion of bacterial functional amyloid requires a bespoke outer-membrane protein channel through which unfolded amyloid substrates are translocated. Here, we combine X-ray crystallography, native mass spectrometry, single-channel electrical recording, molecular simulations and circular dichroism measurements to provide high-resolution structural insight into the functional amyloid transporter from Pseudomonas, FapF...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28782633/plasma-cell-deficiency-in-humans-with-heterozygous-mutations-in-sec61a1
#3
Desirée Schubert, Marie-Christine Klein, Sarah Hassdenteufel, Andrés Caballero-Oteyza, Linlin Yang, Michele Proietti, Alla Bulashevska, Janine Kemming, Johannes Kühn, Sandra Winzer, Stephan Rusch, Manfred Fliegauf, Alejandro A Schäffer, Stefan Pfeffer, Roger Geiger, Adolfo Cavalié, Hongzhi Cao, Fang Yang, Yong Li, Marta Rizzi, Hermann Eibel, Robin Kobbe, Amy L Marks, Brian P Peppers, Robert W Hostoffer, Jennifer M Puck, Richard Zimmermann, Bodo Grimbacher
BACKGROUND: Primary antibody deficiencies (PAD) are the most frequent primary immunodeficiencies in humans. The genetic causes for PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum (ER) membrane. SEC61A1 is a target gene of XBP1s and strongly induced during plasma cell differentiation. OBJECTIVE: Characterization of a novel genetic defect and its pathological mechanism in eleven patients from two unrelated families with PAD...
August 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28776058/sds-assisted-protein-transport-through-solid-state-nanopores
#4
Laura Restrepo-Pérez, Shalini John, Aleksei Aksimentiev, Chirlmin Joo, Cees Dekker
Using nanopores for single-molecule sequencing of proteins - similar to nanopore-based sequencing of DNA - faces multiple challenges, including unfolding of the complex tertiary structure of the proteins and enforcing their unidirectional translocation through nanopores. Here, we combine molecular dynamics (MD) simulations with single-molecule experiments to investigate the utility of SDS (Sodium Dodecyl Sulfate) to unfold proteins for solid-state nanopore translocation, while simultaneously endowing them with a stronger electrical charge...
August 4, 2017: Nanoscale
https://www.readbyqxmd.com/read/28724722/effect-of-directional-pulling-on-mechanical-protein-degradation-by-atp-dependent-proteolytic-machines
#5
Adrian O Olivares, Hema Chandra Kotamarthi, Benjamin J Stein, Robert T Sauer, Tania A Baker
AAA+ proteases and remodeling machines couple hydrolysis of ATP to mechanical unfolding and translocation of proteins following recognition of sequence tags called degrons. Here, we use single-molecule optical trapping to determine the mechanochemistry of two AAA+ proteases, Escherichia coli ClpXP and ClpAP, as they unfold and translocate substrates containing multiple copies of the titin(I27) domain during degradation initiated from the N terminus. Previous studies characterized degradation of related substrates with C-terminal degrons...
July 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28706146/ros-independent-nrf2-activation-in-prostate-cancer
#6
Ilaria Bellezza, Paolo Scarpelli, Salvatore V Pizzo, Silvia Grottelli, Egidia Costanzi, Alba Minelli
In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aiming to restore cellular homeostasis as well as an adaptive survival mechanism. Glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein (GRP78/BiP) is a key molecular chaperone in the endoplasmic reticulum that, when expressed at the cell surface, acts as a receptor for several signaling pathways enhancing antiapoptotic and proliferative signals...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28676851/aaa-atpases-in-protein-degradation
#7
REVIEW
Ravikiran S Yedidi, Petra Wendler, Cordula Enenkel
Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28675036/asymmetric-conformational-transitions-in-aaa-biological-nanomachines-modulate-direction-dependent-substrate-protein-unfolding-mechanisms
#8
Abdolreza Javidialesaadi, George Stan
Powerful AAA+ biological nanomachines, such as ClpY, form hexameric ring structures, which selectively process abnormal proteins targeted for degradation by unfolding and threading them through a narrow central channel. The molecular details of this process are not yet fully understood. We perform Langevin dynamics simulations using a coarse-grained model of substrate proteins (SPs), Titin I27 and its V13P variant, threading through the ClpY pore. We probe the effect of ClpY surface heterogeneity and changes in pore width on SP orientation and the direction of applied force during SP unfolding...
July 27, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28670265/the-endoplasmic-reticulum-unfolded-protein-response-in-neurodegenerative-disorders-and-its-potential-therapeutic-significance
#9
REVIEW
Paolo Remondelli, Maurizio Renna
In eukaryotic cells, the endoplasmic reticulum (ER) is the cell compartment involved in secretory protein translocation and quality control of secretory protein folding. Different conditions can alter ER function, resulting in the accumulation of unfolded or misfolded proteins within the ER lumen. Such a condition, known as ER stress, elicits an integrated adaptive response known as the unfolded protein response (UPR) that aims to restore proteostasis within the secretory pathway. Conversely, in prolonged cell stress or insufficient adaptive response, UPR signaling causes cell death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28624220/tat-hafgf14-154-upregulates-adam10-to-attenuate-the-alzheimer-phenotype-of-app-ps1-mice-through-the-pi3k-creb-ire1%C3%AE-xbp1-pathway
#10
Tian Meng, Qin Cao, Peng Lei, Ashley I Bush, Qi Xiang, Zhijian Su, Xiang He, Jack T Rogers, Ing-Ming Chiu, Qihao Zhang, Yadong Huang
Acid fibroblast growth factor (aFGF) has shown neuroprotection in Alzheimer's disease (AD) models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14-154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14-154 treatment significantly ameliorated behavioral deficits, relieved brain Aβ burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in the brain...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28619716/ratchet-like-polypeptide-translocation-mechanism-of-the-aaa-disaggregase-hsp104
#11
Stephanie N Gates, Adam L Yokom, JiaBei Lin, Meredith E Jackrel, Alexandrea N Rizo, Nathan M Kendsersky, Courtney E Buell, Elizabeth A Sweeny, Korrie L Mack, Edward Chuang, Mariana P Torrente, Min Su, James Shorter, Daniel R Southworth
Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from Saccharomyces cerevisiae solubilizes stress-induced amorphous aggregates and amyloids. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo-electron microscopy structures at near-atomic resolution of Hsp104 in different translocation states...
July 21, 2017: Science
https://www.readbyqxmd.com/read/28583440/proteasome-structure-and-assembly
#12
REVIEW
Lauren Budenholzer, Chin Leng Cheng, Yanjie Li, Mark Hochstrasser
The eukaryotic 26S proteasome is a large multi-subunit complex that degrades the majority of proteins in the cell under normal conditions. The 26S proteasome can be divided into two subcomplexes: the 19S regulatory particle (RP) and the 20S core particle (CP). Most substrates are first covalently modified by ubiquitin, which then directs them to the proteasome. The function of the RP is to recognize, unfold, deubiquitylate and translocate substrates into the CP, which contains the proteolytic sites of the proteasome...
June 2, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28559891/systematic-optimization-of-protein-secretory-pathways-in-saccharomyces-cerevisiae-to-increase-expression-of-hepatitis-b-small-antigen
#13
Jiayuan Sheng, Hunter Flick, Xueyang Feng
Hepatitis B is a major disease that chronically infects millions of people in the world, especially in developing countries. Currently, one of the effective vaccines to prevent Hepatitis B is the Hepatitis B Small Antigen (HBsAg), which is mainly produced by the recombinant yeast Saccharomyces cerevisiae. In order to bring down the price, which is still too high for people in developing countries to afford, it is important to understand key cellular processes that limit protein expression. In this study, we took advantage of yeast knockout collection (YKO) and screened 194 S...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28548229/endoplasmic-reticulum-stress-in-the-heart-the-insights-into-mechanisms-and-drug-targets
#14
REVIEW
Shunyao Wang, Pablo Binder, Qiru Fang, Zhenzhong Wang, Wei Xiao, Wei Liu, Xin Wang
The endoplasmic reticulum (ER) serves several essential cellular functions including protein synthesis, protein folding, protein translocation, calcium homoeostasis and lipid biosynthesis. Physiological or pathological stimuli which disrupt ER homoeostasis and disturb its functions lead to an accumulation of misfolded and unfolded proteins, a condition referred to as ER stress. ER stress triggers unfolded protein response (UPR) to restore the homoeostasis of ER through activating transcriptional and translational pathways...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28475898/molecular-mechanism-of-substrate-processing-by-the-cdc48-atpase-complex
#15
Nicholas O Bodnar, Tom A Rapoport
The Cdc48 ATPase and its cofactors Ufd1/Npl4 (UN) extract polyubiquitinated proteins from membranes or macromolecular complexes, but how they perform these functions is unclear. Cdc48 consists of an N-terminal domain that binds UN and two stacked hexameric ATPase rings (D1 and D2) surrounding a central pore. Here, we use purified components to elucidate how the Cdc48 complex processes substrates. After interaction of the polyubiquitin chain with UN, ATP hydrolysis by the D2 ring moves the polypeptide completely through the double ring, generating a pulling force on the substrate and causing its unfolding...
May 4, 2017: Cell
https://www.readbyqxmd.com/read/28433661/differential-protein-acetylation-assists-import-of-excess-sod2-into-mitochondria-and-mediates-sod2-aggregation-associated-with-cardiac-hypertrophy-in-the-murine-sod2-tg-heart
#16
Liwen Zhang, Chwen-Lih Chen, Patrick T Kang, Zhicheng Jin, Yeong-Renn Chen
SOD2 is the primary antioxidant enzyme neutralizing (•)O2(-) in mitochondria. Cardiac-specific SOD2 overexpression (SOD2-tg) induces supernormal function and cardiac hypertrophy in the mouse heart. However, the reductive stress imposed by SOD2 overexpression results in protein aggregation of SOD2 pentamers and differential hyperacetylation of SOD2 in the mitochondria and cytosol. Here, we studied SOD2 acetylation in SOD2-tg and wild-type mouse hearts. LC-MS/MS analysis indicated the presence of four acetylated lysines in matrix SOD2 and nine acetylated lysines in cytosolic SOD2 from the SOD2-tg heart...
July 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28421184/the-proteasomal-atpases-use-a-slow-but-highly-processive-strategy-to-unfold-proteins
#17
Aaron Snoberger, Raymond T Anderson, David M Smith
All domains of life have ATP-dependent compartmentalized proteases that sequester their peptidase sites on their interior. ATPase complexes will often associate with these compartmentalized proteases in order to unfold and inject substrates into the protease for degradation. Significant effort has been put into understanding how ATP hydrolysis is used to apply force to proteins and cause them to unfold. The unfolding kinetics of the bacterial ATPase, ClpX, have been shown to resemble a fast motor that traps unfolded intermediates as a strategy to unfold proteins...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28419599/mycobacterium-tuberculosis-proteasomal-atpase-mpa-has-a-%C3%AE-grasp-domain-that-hinders-docking-with-the-proteasome-core-protease
#18
Yujie Wu, Kuan Hu, Defeng Li, Lin Bai, Shaoqing Yang, Jordan B Jastrab, Shuhao Xiao, Yonglin Hu, Susan Zhang, K Heran Darwin, Tao Wang, Huilin Li
Mycobacterium tuberculosis (Mtb) has a proteasome system that is essential for its ability to cause lethal infections in mice. A key component of the system is the proteasomal adenosine triphosphatase (ATPase) Mpa, which captures, unfolds, and translocates protein substrates into the Mtb proteasome core particle for degradation. Here, we report the crystal structures of near full-length hexameric Mtb Mpa in apo and ADP-bound forms. Surprisingly, the structures revealed a ubiquitin-like β-grasp domain that precedes the proteasome-activating carboxyl terminus...
July 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28417122/frequency-control-of-protein-translocation-across-an-oscillating-nanopore
#19
Fabio Cecconi, Muhammad Adnan Shahzad, Umberto Marini Bettolo Marconi, Angelo Vulpiani
The translocation of a lipid binding protein (LBP) is studied using a phenomenological coarse-grained computational model that simplifies both chain and pore geometry. We investigated via molecular dynamics the interplay between transport and unfolding in the presence of a nanopore whose section oscillates periodically in time with a frequency ω, a motion often referred to as the radial breathing mode (RBM). We found that the LPB when mechanically pulled into the vibrating nanopore exhibits a translocation dynamics that in some frequency range is accelerated and shows a frequency locking to the pore dynamics...
April 18, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28407373/activation-of-the-arabidopsis-membrane-bound-transcription-factor-bzip28-is-mediated-by-site-2-protease-but-not-site-1-protease
#20
Yuji Iwata, Makoto Ashida, Chisa Hasegawa, Kazuki Tabara, Kei-Ichiro Mishiba, Nozomu Koizumi
The unfolded protein response (UPR) is a homeostatic cellular response conserved in eukaryotic cells to alleviate the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Arabidopsis bZIP28 is a membrane-bound transcription factor activated by proteolytic cleavage in response to ER stress, thereby releasing its cytosolic portion containing the bZIP domain from the membrane to translocate into the nucleus where it induces the transcription of genes encoding ER-resident molecular chaperones and folding enzymes...
August 2017: Plant Journal: for Cell and Molecular Biology
keyword
keyword
95523
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"