Abstract：
:The clarification of the physico-chemical determinants underlying amyloid deposition is critical for our understanding of misfolding diseases. With this purpose we have performed a systematic all-atom molecular dynamics (MD) study of a series of single point mutants of the de novo designed amyloidogenic peptide STVIIE. Sixteen different 50ns long simulations using explicit solvent have been carried out starting from four different conformations of a polymeric six-stranded beta-sheet. The simulations have provided evidence for the influence of a small number of site-specific hydrophobic interactions on the packing and stabilization of nascent aggregates, as well as the interplay between side-chain interactions and the net charge of the molecule on the strand arrangement of polymeric beta-sheets. This MD analysis has also shed light into the origin of the position dependence on mutation of beta-sheet polymerization that was found experimentally for this model system. Our results suggest that MD can be applied to detect critical positions for beta-sheet aggregation within a given amyloidogenic stretch. Studies similar to the one presented here can guide site-directed mutations or the design of drugs that specifically disrupt the key stabilizing interactions of beta-sheet aggregates.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
López de la Paz M,de Mori GM,Serrano L,Colombo Gdoi
10.1016/j.jmb.2005.03.081keywords:
subject
Has Abstractpub_date
2005-06-10 00:00:00pages
583-96issue
3eissn
0022-2836issn
1089-8638pii
S0022-2836(05)00383-9journal_volume
349pub_type
杂志文章abstract：:The structure of empty canine parvovirus capsids shows that residues 37 to the carboxy-terminal residue 584 (VP2 numbering) are ordered in each of the 60 subunits. The central structural motif of each subunit is the eight-stranded antiparallel beta-barrel that has been found in many other virus structures. Five beta-h...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1993.1502
更新日期：1993-09-20 00:00:00
abstract：:We propose a general classification scheme for loops, aperiodic segments of protein structure. In an effort to avoid the geometric complexity created by non-repeating phi psi angles, a morphologic definition that focuses upon the linearity and planarity of loops is utilized. Out of 432 loops (4 to 20 residues in lengt...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(92)90553-v
更新日期：1992-04-05 00:00:00
abstract：:The outer membrane usher protein Caf1A of the plague pathogen Yersinia pestis is responsible for the assembly of a major surface antigen, the F1 capsule. The F1 capsule is mainly formed by thin linear polymers of Caf1 (capsular antigen fraction 1) protein subunits. The Caf1A usher promotes polymerization of subunits a...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2010.08.034
更新日期：2010-10-22 00:00:00
abstract：:Riboswitches are noncoding RNA elements that are commonly found in the 5'-untranslated region of bacterial mRNA. Binding of a small-molecule metabolite to the riboswitch aptamer domain guides the folding of the downstream sequence into one of two mutually exclusive secondary structures that directs gene expression. Th...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.10.074
更新日期：2009-01-23 00:00:00
abstract：:Siderophores are small-molecule iron chelators that many bacteria synthesize and secrete in order to survive in iron-depleted environments. Biosynthesis of enterobactin, the Escherichia coli catecholate siderophore, requires adenylation of 2,3-dihydroxybenzoic acid (2,3-DHB) by the cytoplasmic enzyme EntE. The DHB-AMP...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.08.036
更新日期：2009-10-30 00:00:00
abstract：:To gain an understanding of structural changes induced in substrates by Escherichia coli ribonuclease P (RNase P), we have incorporated an interstrand disulfide crosslink proximal to the cleavage site in a model substrate. RNase P is able to process the reduced, non-crosslinked form of this substrate as well as a subs...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.3424
更新日期：2000-02-04 00:00:00
abstract：:The 37-residue Formin-binding protein, FBP28, is a canonical three-stranded beta-sheet WW domain. Because of its small size, it is so insensitive to chemical denaturation that it is barely possible to determine accurately a denaturation curve, as the transition spans 0-7 M guanidinium hydrochloride (GdmCl). It is also...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.05.050
更新日期：2006-07-21 00:00:00
abstract：:The ligation of a decadeoxynucleotide containing the EcoRI recognition site forms a series of multimers which appear to be curved based on observed anomalous gel migration in polyacrylamide gels. The degree of DNA curvature present in the recognition sequence, based upon the observed migration anomaly, can be altered ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(88)90561-x
更新日期：1988-08-20 00:00:00
abstract：:Through the high-resolution structure of the gramicidin A channel in lamellar phase lipids and the characterization of specific ion peptide interactions, fundamental principles for ion channel selectivity and conductance efficiency are illustrated with atomic resolution detail. Delocalized cation binding in the first ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2434
更新日期：1999-02-05 00:00:00
abstract：:We find that tRNA gene transcription is controlled by a region much larger than the previously described internal segments known as A and B boxes. In a Bombyx mori silkworm tRNA2Ala gene, transcriptionally important sequences extend at least from -13 to +146, and thus include sequences both upstream and downstream fro...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(85)90209-8
更新日期：1985-05-25 00:00:00
abstract：:The energetic profiles of a significant number of protein-DNA systems at 20 degrees C reveal that, despite comparable Gibbs free energies, association with the major groove is primarily an enthalpy-driven process, whereas binding to the minor groove is characterized by an unfavorable enthalpy that is compensated by fa...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2006.09.059
更新日期：2007-01-05 00:00:00
abstract：:The crystal and molecular structure of a triacylglyceride lipase (EC 3.1.1.3) from the fungus Rhizomucor miehei was analyzed using X-ray single crystal diffraction data to 1.9 A resolution. The structure was refined to an R-factor of 0.169 for all available data. The details of the molecular architecture and the cryst...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(92)90225-9
更新日期：1992-10-05 00:00:00
abstract：:The bacterial immunity proteins Im7 and Im9 fold with mechanisms of different kinetic complexity. Whilst Im9 folds in a two-state transition at pH 7.0 and 10 degrees C, Im7 populates an on-pathway intermediate under these conditions. In order to assess the role of sequence versus topology in the folding of these prote...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(02)01249-4
更新日期：2003-02-07 00:00:00
abstract：:Tumor suppressor p53 plays a central role in tumor suppression. p53 is the most frequently mutated gene in human cancer, and over half of human cancers contain p53 mutations. Majority of p53 mutations in cancer are missense mutations, leading to the expression of full-length mutant p53 (mutp53) protein. While the crit...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2017.03.030
更新日期：2017-06-02 00:00:00
abstract：:The molecular chaperone Hsp90 is essential for the correct folding, maturation and activation of a diverse array of client proteins, including several key constituents of oncogenic processes. Hsp90 has become a focus of cancer research, since it represents a target for direct prophylaxis against multistep malignancy. ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.04.059
更新日期：2007-10-05 00:00:00
abstract：:The main regulator of pIP501 replication is an antisense RNA (RNAIII) that induces transcriptional attenuation of the essential RNAII. Previous studies identified the termination point in vivo and demonstrated attenuation in vitro. This in vivo analysis confirms the appearance of attenuated RNAII dependent on RNAIII. ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0023
更新日期：1996-01-19 00:00:00
abstract：:In bacteriophages of the cystovirus family, the polymerase complex (PX) encodes a 75-kDa RNA-directed RNA polymerase (P2) that transcribes the double-stranded RNA genome. Also a constituent of the PX is the essential protein P7 that, in addition to accelerating PX assembly and facilitating genome packaging, plays a re...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2014.04.028
更新日期：2014-07-15 00:00:00
abstract：:Identifying the complete set of transcription factors that bind the promoter and other regulatory regions of a gene of interest is an essential step in functional genomics. We have developed an original assay for the systematic detection of hepatocyte nuclear factor-3 (HNF-3) binding sites within cloned promoters. Thi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.4788
更新日期：2001-07-13 00:00:00
abstract：:The Hippo pathway plays a crucial role in growth control, proliferation and tumor suppression. Activity of the signaling pathway is associated with cell density sensing and tissue organization. Furthermore, the Hippo pathway helps to coordinate cellular processes through crosstalk with growth-factor-mediated signaling...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2015.04.015
更新日期：2015-10-23 00:00:00
abstract：:Forkhead box O4 (FOXO4) is a human transcription factor (TF) that participates in cell homeostasis. While the structure and DNA binding properties of the conserved forkhead domain (FHD) have been thoroughly investigated, how the transactivation domain (TAD) regulates the DNA binding properties of the protein remains e...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2021.166808
更新日期：2021-01-13 00:00:00
abstract：:The transcriptional repressor CopR is one of the two copy-number control components of plasmid pIP501. CopR binds as a dimer at two consecutive major grooves on the same face of the DNA. Previously, equilibrium dissociation constants of CopR dimers and the CopR-DNA complex and the intracellular CopR concentration were...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.3929
更新日期：2000-07-28 00:00:00
abstract：:We investigate the suggestion that aromatic rings can act as hydrogen-bond acceptors in proteins, by an analysis of 55 non-homologous high-resolution protein chain structures. Approximately 10% of interactions between sp2 hybridized nitrogen atoms, from either side-chains or main-chains, and phenylalanine or tyrosine ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1370
更新日期：1994-06-03 00:00:00
abstract：:The nucleotide sequence of 6.2 kb (1 kb = 10(3) base-pairs) of DNA that encompasses the earliest replicating portion of the amplified dihydrofolate reductase domains of CHOC 400 cells has been determined. Origin region DNA contains two AluI family repeats, a novel repetitive element (termed ORR-1), a TGGGT-rich region...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(90)90008-A
更新日期：1990-01-05 00:00:00
abstract：:Cytochrome c oxidase couples the reduction of dioxygen to proton pumping against an electrochemical gradient. The D-channel, a 25-A-long cavity, provides the principal pathway for the uptake of chemical and pumped protons. A water chain is thought to mediate the relay of protons via a Grotthuss mechanism through the D...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.02.042
更新日期：2009-04-17 00:00:00
abstract：:We present a refined model of the membrane-associated Torpedo acetylcholine (ACh) receptor at 4A resolution. An improved experimental density map was obtained from 342 electron images of helical tubes, and the refined structure was derived to an R-factor of 36.7% (R(free) 37.9%) by standard crystallographic methods, a...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.12.031
更新日期：2005-03-04 00:00:00
abstract：:One of the last uncharted territories in evolutionary biology concerns the link with cell biology. Because all phenotypes ultimately derive from events at the cellular level, this connection is essential to building a mechanism-based theory of evolution. Given the impressive developments in cell biological methodologi...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2020.02.006
更新日期：2020-03-27 00:00:00
abstract：:The crystal structure of the eubacteria Mycoplasma genitalium ORF MG438 polypeptide, determined by multiple anomalous dispersion and refined at 2.3 A resolution, reveals the organization of S subunits from the Type I restriction and modification system. The structure consists of two globular domains, with about 150 re...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.06.050
更新日期：2005-08-26 00:00:00
abstract：:Endospore formation in Bacillus subtilis is orchestrated by five developmental sigma factors and further modulated by several auxiliary transcription factors. One of these, SpoVT, regulates forespore-specific sigma(G)-dependent genes and plays a key role in the final stages of spore formation. We have determined the c...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.10.061
更新日期：2009-03-06 00:00:00
abstract：:The adaptor protein Tks5/FISH (tyrosine kinase substrate 5/five SH3 domains, hereafter termed Tks5) is a crucial component of a protein network that controls the invasiveness of cancer cells and progression of Alzheimer's disease. Tks5 consists of an amino-terminal PX domain that is followed by five SH3 domains (SH3A-...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.05.025
更新日期：2009-07-31 00:00:00
abstract：:RNA virus behavior can be influenced by interactions among viral genomes and their expression products within the mutant spectra of replicating viral quasispecies. Here, we report the extent of interference of specific capsid and polymerase mutants of foot-and-mouth disease virus (FMDV) on replication of wild-type (wt...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.03.074
更新日期：2007-06-15 00:00:00
