Abstract：
:Neurons are electrically excitable, postmitotic cells that perform sensory, relaying, and motor functions. Because of their unique morphological and functional specialization, cells of this type are sensitive to the stress caused by accumulation of misfolded proteins or damaged organelles. Autophagy is the fundamental mechanism that ensures sequestration of cytosolic material and its subsequent degradation in lysosomes of eukaryotic cells, thereby providing cell-autonomous nutrients and removing harmful cargos. Strikingly, mice and flies lacking functional autophagy develop early onset progressive neurodegeneration. Like in human neurodegenerative diseases (NDDs)-Alzheimer's disease, Parkinson's disease, frontotemporal dementia, Huntington's disease, and amyotrophic lateral sclerosis-characteristic protein aggregates observed in autophagy-deficient neurons in the animal models are indicators of the ongoing neuronal pathology. A number of selective autophagy receptors (SARs) have been characterized that interact both with the cargo and components of the autophagic machinery, thus providing the molecular basis for selective degradation of sizable cytosolic components. Interference with autophagy in experimental models, but also during the pathological vagaries in neurons, will thus have far-reaching consequences for a range of selective autophagy pathways critical for the normal functioning of the nervous system. Here, we review the key principles behind the selective autophagy and discuss how the SARs may be involved in the pathogenesis of NDDs. Using recently published examples, we also examine the emerging role of less well studied selective autophagy pathways in neuronal health and disease. We conclude by discussing targeting selective autophagy as an emerging therapeutic modality in NDDs.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Conway O,Akpinar HA,Rogov VV,Kirkin Vdoi
10.1016/j.jmb.2019.10.013subject
Has Abstractpub_date
2020-04-03 00:00:00pages
2483-2509issue
8eissn
0022-2836issn
1089-8638pii
S0022-2836(19)30609-6journal_volume
432pub_type
杂志文章,评审abstract：:A 144 amino acid residue cts-52 mutant repressor (mtc phi 105) located in the EcoRI-F immunity region (immF) of Bacillus subtilis phage phi 105 is involved in the control mechanism of a thermo-inducible expression system. Adjacent to the repressor gene, an open-reading frame, designated ORF4, encodes a polypeptide of ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2003.08.017
更新日期：2003-10-10 00:00:00
abstract：:The pentameric ATPase motor gp16 packages double-stranded DNA into the bacteriophage phi29 virus capsid. On the basis of the results of single-molecule experimental studies, we propose a push and roll mechanism to explain how the packaging motor translocates the DNA in bursts of four 2.5 bp power strokes, while rotati...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2010.05.002
更新日期：2010-07-09 00:00:00
abstract：:The cobalamin-independent methionine synthase enzyme catalyzes a challenging reaction: the direct transfer of a methyl from 5-methyl-tetrahydrofolate-glutamate3 to the l-homocysteine thiol. The enzyme has a dual (βα)8 TIM barrel structure that binds, activates and brings the reactants into reaction proximity by confor...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2014.12.014
更新日期：2015-02-27 00:00:00
abstract：:We identified the predominant 5' ends of an mRNA in Escherichia coli to the exact nucleotides. There are four such ends of lac mRNA in fully induced cells. About 70% of the molecules have the reported major in vitro end, A-A-U-U-G (at +1), which is located 38 nucleotides before the A-U-G translation start. Another 15%...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(85)90342-0
更新日期：1985-03-20 00:00:00
abstract：:A pre-condition for the ab initio assignment of Euler angles to a set of projections from an asymmetric object is that at least three of the available projections correspond to rotations about different axes. For symmetric objects this condition may be relaxed. There are some applications of single-particle electron m...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.09.068
更新日期：2004-11-26 00:00:00
abstract：:The MCM motor of the CMG helicase powers ahead of the eukaryotic replication machinery to unwind DNA, in a process that requires ATP hydrolysis. The reconstitution of DNA replication in vitro has established the succession of events that lead to replication origin activation by the MCM and recent studies have started ...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2016.01.024
更新日期：2016-05-08 00:00:00
abstract：:Phage display, SELEX and other methods of combinatorial chemistry have become very popular means of finding ligands with high affinities to given targets. Despite their success, they suffer from numerous sources of error and bias, such as very low initial concentrations of species, non-specific binding, and the sampli...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1997.1555
更新日期：1998-04-10 00:00:00
abstract：:Natural cellulose exists as a composite of different forms, which have historically been broadly characterized as "crystalline" or "amorphous". The recognition of both of these forms of cellulose by the carbohydrate-binding modules (CBM) of microbial glycoside hydrolases is central to natural and efficient biotechnolo...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.03.069
更新日期：2004-05-28 00:00:00
abstract：:Arc repressor from bacteriophage P22 is a homodimeric member of the ribbon-helix-helix family of transcription factors. Two dimers bind cooperatively to adjacent sites on operator DNA with the antiparallel beta-sheet of each Arc dimer contacting the major groove. Despite the 2-fold symmetry of the dimer, the sequence ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.04.026
更新日期：2004-07-02 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.04.077
更新日期：2009-06-26 00:00:00
abstract：:Normal type I collagen is a heterotrimer of two alpha1(I) and one alpha2(I) chains, but various genetic and environmental factors result in synthesis of homotrimers that consist of three alpha1(I) chains. The homotrimers completely replace the heterotrimers only in rare recessive disorders. In the general population, ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.08.008
更新日期：2008-10-31 00:00:00
abstract：:The β-lactams retain a central place in the antibacterial armamentarium. In Gram-negative bacteria, β-lactamase enzymes that hydrolyze the amide bond of the four-membered β-lactam ring are the primary resistance mechanism, with multiple enzymes disseminating on mobile genetic elements across opportunistic pathogens su...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2019.04.002
更新日期：2019-08-23 00:00:00
abstract：:Islet amyloid polypeptide (IAPP) is an unstructured polypeptide hormone that is cosecreted with insulin. In patients with type 2 diabetes, IAPP undergoes a transition from its natively disordered state to a highly ordered, all-beta-strand amyloid fiber. Although predominantly disordered, IAPP transiently samples alpha...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.07.077
更新日期：2009-10-23 00:00:00
abstract：:The beta-globin gene cluster of human, gorilla and chimpanzee contain the same number and organization of beta-type globin genes: 5'-epsilon (embryonic)-G gamma and A gamma (fetal)-psi beta (inactive)-delta and beta (adult)-3'. We have isolated the psi beta-globin gene regions from the three species and determined the...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(84)90256-0
更新日期：1984-12-25 00:00:00
abstract：:Nitrite reductase from Pseudomonas aeruginosa (EC 1.9.3.2), a redox enzyme synthesized by the bacterium grown in the presence of nitrate, is a soluble dimer of two identical subunits of 60 kDa, each containing one c and one d1 haem as prosthetic groups. A new crystal from of the Ps. aeruginosa nitrite reductase in the...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1659
更新日期：1994-10-21 00:00:00
abstract：:We have examined the structure of hemoglobin S fibers, which are associated into large bundles, or fascicles. Electron micrographs of embedded and cross-sectioned fascicles provide an end-on view of the component fibers. The cross-sectional images are rotationally blurred as a result of the twist of the fiber within t...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(88)90322-1
更新日期：1988-01-20 00:00:00
abstract：:Membranes have a potent ability to promote secondary structure formation in a wide range of membrane-active peptides, believed to be due to a reduction through hydrogen bonding of the energetic cost of partitioning peptide bonds. This process is of fundamental importance for understanding the mechanism of action of to...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2346
更新日期：1999-01-29 00:00:00
abstract：:The solvent-accessible surface area (As) of 23 oligomeric proteins is calculated using atomic co-ordinates from high-resolution and well-refined crystal structures. As is correlated with the protein molecular weight, and a power law predicts its value to within 5% on average. The accessible surface of the average olig...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(88)90606-7
更新日期：1988-11-05 00:00:00
abstract：:In the presence of AMP-PCP (beta, gamma-methyleneadenosine 5'-triphosphate), a non-hydrolyzable analog of ATP, negative stain images of increased morphological detail indicate that the dynein arm, attached to ciliary doublet microtubules, is composed of subunits including a cape, an elongated body and a head. The arra...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(84)90127-x
更新日期：1984-03-05 00:00:00
abstract：:Escherichia coli PriA is a primosome assembly protein with 3' to 5' helicase activity whose apparent function is to promote resumption of DNA synthesis following replication-fork arrest. Here, we describe how initiation of helicase activity on DNA forks is influenced by both fork structure and by single-strand DNA-bin...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.4930
更新日期：2001-10-05 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.12.043
更新日期：2006-03-24 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.3404
更新日期：2000-01-28 00:00:00
abstract：:Bacteriophages are involved in many aspects of the spread and establishment of virulence factors in Staphylococcus aureus, including the mobilization of genetic elements known as S. aureus pathogenicity islands (SaPIs), which carry genes for superantigen toxins and other virulence factors. SaPIs are packaged into phag...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2010.11.047
更新日期：2011-01-21 00:00:00
abstract：:The activator protein-1 (AP-1) complex plays a crucial role in numerous pathways, and its ability to induce tumorigenesis is well documented. Thus, AP-1 represents an interesting therapeutic target. We selected peptides from phage display and compared their ability to disrupt the cFos/cJun interaction to a previously ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.04.030
更新日期：2008-08-01 00:00:00
abstract：:Bacteriophage P4 immunity is controlled by a small stable RNA (CI RNA) that derives from the processing of primary transcripts. In previous works, we observed that the endonuclease RNase P is required for the maturation of CI RNA 5'-end; moreover, we found that polynucleotide phosphorylase (PNPase), a 3' to 5' RNA-deg...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/S0022-2836(02)00085-2
更新日期：2002-04-26 00:00:00
abstract：:Sequences flanking the protein-coding regions of 15 of the 17 to 20 actin genes in the cellular slime mold Dictyostelium discoidium have been determined. Comparison of sequences among genes shows that they contain extensive homologies at both the 5' and 3' ends of the coding regions. On the basis of these homologies, ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(85)90003-8
更新日期：1985-06-05 00:00:00
abstract：:The deposition of alpha-synuclein (alpha-syn) aggregates in dopaminergic neurons is a key feature of Parkinson's disease. While dopamine (DA) can modulate alpha-syn aggregation, it is unclear which other factors can regulate the actions of DA on alpha-syn. In this study, we investigated the effect of solution conditio...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.02.007
更新日期：2009-04-03 00:00:00
abstract：:SHP, the capsid-stabilizing protein of lambdoid phage 21, is highly resistant against denaturant-induced unfolding. We demonstrate that this high functional stability of SHP is due to a high kinetic stability with a half-life for unfolding of 25 days at zero denaturant, while the thermodynamic stability is not unusual...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.09.030
更新日期：2004-11-12 00:00:00
abstract：:Crystal structures of Bacillus stearothermophilus TRS40 neopullulanase and its complexes with panose, maltotetraose and isopanose were determined at resolutions of 1.9, 2.4, 2.8 and 3.2A, respectively. Since the latter two carbohydrates are substrates of this enzyme, a deactivated mutant at the catalytic residue Glu35...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(02)01402-x
更新日期：2003-02-07 00:00:00
abstract：:S100P is a small calcium-binding protein of the S100 EF-hand-containing family of proteins. Elevated levels of its mRNA are reported to be associated with the progression to hormone independence and metastasis of prostate cancer and to be associated with loss of senescence in human breast epithelial cells in vitro. Th...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(02)01278-0
更新日期：2003-01-24 00:00:00
