Abstract：
:The dominant assumption central to most treatments for sickle cell anemia has been that replacement of sickle hemoglobin (HbS) by fetal hemoglobin (HbF) would have major clinical benefit. Using laser photolysis, we have measured polymerization kinetics including rates of homogeneous and heterogeneous nucleation on mixtures of 20% and 30% HbF with HbS. We find that the present model for polymerization, including molecular crowding, can accurately predict the rates of such mixtures, by using the single assumption that no significant amount of HbF enters the polymer. The effects of replacing HbS by HbF on the rates of polymer formation are found to be significantly lower than previous measurements appeared to indicate because the impact of the replacement is also highly dependent on the total hemoglobin concentration. This is because the molecular crowding of non-polymerizing HbF offsets substantially the effects of decreasing the concentration of HbS concentration, an effect that increases with concentration. Most strikingly, the demonstrated benefit of hydroxyurea therapy in slowing the kinetics of intracellular polymerization cannot be primarily due to enhanced HbF, but must have some other origin, which could itself represent a promising therapeutic approach.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Rotter M,Aprelev A,Adachi K,Ferrone FAdoi
10.1016/j.jmb.2005.02.006keywords:
subject
Has Abstractpub_date
2005-04-15 00:00:00pages
1015-23issue
5eissn
0022-2836issn
1089-8638pii
S0022-2836(05)00159-2journal_volume
347pub_type
杂志文章abstract：:The PHD finger and the bromodomain are small protein domains that occur in many proteins associated with phenomena related to chromatin. The bromodomain has been shown to bind acetylated lysine residues on histone tails. Lysine acetylation is one of several histone modifications that have been proposed to form the bas...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.01.051
更新日期：2004-04-02 00:00:00
abstract：:LC3-associated phagocytosis (LAP) is a novel form of non-canonical autophagy where LC3 (microtubule-associated protein 1A/1B-light chain 3) is conjugated to phagosome membranes using a portion of the canonical autophagy machinery. The impact of LAP to immune regulation is best characterized in professional phagocytes,...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2017.08.012
更新日期：2017-11-24 00:00:00
abstract：:The Fv fragment from an anti-dansyl antibody was optimally crystallized into two crystal forms having slightly different lattice dimensions at pH 5.25 and 6.75. The two crystal structures were determined and refined at high resolution at 112 K (at 1.45 A for the crystal at pH 5.25 and at 1.55 A for that at pH 6.75). I...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.2931
更新日期：1999-08-06 00:00:00
abstract：:Using a human non-immune phage library comprising more than 10(9) functional human antibody specificities in Fab format, we have been able to select a set of eight monoclonal Fabs targeted against diverse epitopes of the ectodomain of gp41 from HIV-1. The antigens used for panning the antibodies comprised two soluble,...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.09.044
更新日期：2005-11-11 00:00:00
abstract：:GTP and Ca2+, two well-known modulators of intracellular signaling pathways, control a structural/functional switch between two vital and mutually exclusive activities, cross-linking and Galpha activity, in the same enzyme. The enzyme, a brain-derived tissue-type transglutaminase (TGase), was recently cloned by us in ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2052
更新日期：1998-10-02 00:00:00
abstract：:We have developed a new method for the prediction of peptide sequences that bind to a protein, given a three-dimensional structure of the protein in complex with a peptide. By applying a recently developed sequence prediction algorithm and a novel ensemble averaging calculation, we generate a diverse collection of pep...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.5035
更新日期：2001-10-19 00:00:00
abstract：:To elucidate the general constraints imposed on the structure of the D and T-loops in functional tRNAs, active suppressor tRNAs were selected in vivo from a combinatorial tRNA gene library in which several nucleotide positions in these loops were randomized. Analysis of the nucleotide sequences of the selected clones ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.08.025
更新日期：2004-10-08 00:00:00
abstract：:The homotetrameric Escherichia coli single-stranded DNA binding protein (SSB) plays a central role in DNA replication, repair and recombination. E. coli SSB can bind to long single-stranded DNA (ssDNA) in multiple binding modes using all four subunits [(SSB)65 mode] or only two subunits [(SSB)35 binding mode], with th...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2014.12.020
更新日期：2015-02-27 00:00:00
abstract：:Natural killer (NK) cells play a crucial role in the detection and destruction of virally infected and tumor cells during innate immune responses. The cytolytic activity of NK cells is regulated through a balance of inhibitory and stimulatory signals delivered by NK receptors that recognize classical major histocompat...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(02)00498-9
更新日期：2002-07-12 00:00:00
abstract：:Transcriptional pausing by RNA polymerase has been the subject of extensive investigations in vitro, yet little is known about its occurrence and significance in vivo. The transient nature of the pausing events makes them difficult to observe inside the cell, whereas their studies in vitro by classical biochemical met...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.05.052
更新日期：2005-08-05 00:00:00
abstract：:The vertebrate striated muscle protein titin is thought to play a critical rôle in myofibril assembly and passive tension. The recently determined complete primary structure of titin revealed a modular architecture that opens the way to a structural characterisation and the understanding of essential properties of thi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0050
更新日期：1996-02-02 00:00:00
abstract：:Functional large ribosomal subunits of Thermus aquaticus can be reconstituted from ribosomal proteins and either natural or in vitro transcribed 23 S and 5 S rRNA. Omission of 5 S rRNA during subunit reconstitution results in dramatic decrease of the peptidyl transferase activity of the assembled subunits. However, th...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.3030
更新日期：1999-09-03 00:00:00
abstract：:The regulation of crystal morphology by proteins is often observed in biology. It is a central feature in the formation of hard tissues such as bones, teeth and mollusc shells. We have developed a genetic system in the bacterium Escherichia coli to study the protein-mediated control of crystal growth. We have used the...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.3682
更新日期：2000-06-09 00:00:00
abstract：:Based on structural analyses and on the behavior of mutants, we suggest that the polymerase domain of HIV-1 reverse transcriptase (RT) plays a critical role in holding and appropriately positioning the template-primer both at the polymerase active site and at the RNase H active site. For RT to successfully copy the vi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.1624
更新日期：1998-04-03 00:00:00
abstract：:The structure of tobacco mosaic virus (TMV) has been determined by fiber diffraction methods at 2.9 A resolution, and refined by restrained least-squares to an R-factor of 0.096. Protein-nucleic acid interactions are clearly visible. The final model contains all of the non-hydrogen atoms of the RNA and the protein, 71...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(89)90391-4
更新日期：1989-07-20 00:00:00
abstract：:We use a coarse-grained protein model to characterize the critical nucleus, structural stability, and fibril elongation propensity of Abeta(1-40) oligomers for the C(2x) and C(2z) quaternary forms proposed by solid-state NMR. By estimating equilibrium populations of structurally stable and unstable protofibrils, we de...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.10.011
更新日期：2007-01-12 00:00:00
abstract：:Conformationally constrained environment-dependent amino acid residue substitution tables have been constructed from a database comprising 33 homologous families of protein sequences aligned on the basis of their three-dimensional structures. Residues are allotted to one of 216 (or 54) classes of combinations of struc...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1993.1018
更新日期：1993-01-05 00:00:00
abstract：:Terminases of double-stranded DNA bacteriophages are required for packaging and generation of terminii in replicated concatemeric DNA molecules. Genetic evidence suggests that these functions in phage T4 are carried out by the products of genes 16 and 17. We cloned these T4 genes into a heat-inducible cI repressor-lam...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(88)90537-2
更新日期：1988-04-05 00:00:00
abstract：:Two types of annelid collagens of different sizes were purified, one from acetic acid extracts of the cuticle (length 2.5 microns) and the other, after pepsin digestion, from interstitial spaces of the body wall (0.3 micron). They were obtained from Alvinella pompejana, Alvinella caudata and Paralvinella grasslei coll...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.0084
更新日期：1995-02-17 00:00:00
abstract：:We have probed the structure of the human mitochondrial DNA helicase, an enzyme that uses the energy of nucleotide hydrolysis to unwind duplex DNA during mitochondrial DNA replication. This novel helicase shares substantial amino acid sequence and functional similarities with the bacteriophage T7 primase-helicase. We ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.01.079
更新日期：2007-04-13 00:00:00
abstract：:Clathrin-coated vesicles mediate vesicular traffic in cells. Three-dimensional image reconstructions of homogenous populations of in vitro assembled clathrin coats have yielded a molecular model for clathrin and its interactions with some of its partners. The intrinsic averaging required for those calculations has pre...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.10.036
更新日期：2007-01-19 00:00:00
abstract：:Activation of family A G-protein-coupled receptors involves a rearrangement of a conserved interhelical cytoplasmic hydrogen bond network between the E(D)RY motif on transmembrane helix 3 (H3) and residues on H6, which is commonly termed the cytoplasmic "ionic lock." Glu134(3.49) of the E(D)RY motif also forms an intr...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.05.022
更新日期：2008-07-18 00:00:00
abstract：:A new method is suggested here for topology prediction of helical transmembrane proteins. The method is based on the hypothesis that the localizations of the transmembrane segments and the topology are determined by the difference in the amino acid distributions in various structural parts of these proteins rather tha...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2107
更新日期：1998-10-23 00:00:00
abstract：:The detection of conserved sequence patterns (motifs) in related proteins often yields valuable structural and functional insights. We describe a method that utilizes rigorous statistics and a depth-first search procedure to efficiently and exhaustively search a set of proteins for significant patterns up to a specifi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1407
更新日期：1994-06-24 00:00:00
abstract：:Historically referred to as "the GTPase center", the L11 binding region (L11BR) of Escherichia coli 23 S rRNA is a highly conserved structure that has been implicated in several essential functions during protein synthesis. Here, in vivo expression of an RNA fragment containing that structure was found to affect trans...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/S0022-2836(02)00304-2
更新日期：2002-05-31 00:00:00
abstract：:The preferred DNase I cleavage sites within the 160 bp tyrT DNA fragment were identified by studying the initial rate of cleavage of individual bonds. The results show that there is no correlation between the rate of cleavage and the identity of the dinucleotide sequence that is cleaved. Examination of the sequences s...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1152
更新日期：1994-02-18 00:00:00
abstract：:Phosphorylation of short linear peptide motifs is a widespread process for the dynamic regulation of protein-protein interactions. However, the global impact of phosphorylation events on the protein-protein interactome is rarely addressed. The disordered C-terminal tail of ribosomal S6 kinase 1 (RSK1) binds to PDZ dom...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2019.01.038
更新日期：2019-03-15 00:00:00
abstract：:A combination of experimental structural data, homology modelling and elastic network normal mode analysis is used to explore how coupled motions between the two myosin heads and the dimerization domain (S2) in smooth muscle myosin II determine the domain movements required to achieve the inhibited state of this ATP-d...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.10.084
更新日期：2005-01-28 00:00:00
abstract：:A parallel stacking arrangement of the guanidinium groups of arginines directly over the center of the rings of aromatic side-chains is observed much more frequently in proteins than would be expected by chance. This type of interaction, which is often found in locations critical to the function, apparently serves to ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1022
更新日期：1994-01-14 00:00:00
abstract：:Protein acetylation plays important roles in many biological processes. Malate dehydrogenase (MDH), a key enzyme in the tricarboxylic acid cycle, has been identified to be acetylated in bacteria by proteomic studies, but no further characterization has been reported. One challenge for studying protein acetylation is t...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2017.03.027
更新日期：2017-05-05 00:00:00
