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, they may compose just a small fraction of type I collagen. Nevertheless, they may play a significant role in pathology; for example, synthesis of 10-15% homotrimers due to a polymorphism in the alpha1(I) gene may contribute to osteoporosis. Homotrimer triple helices have different stability and less efficient fibrillogenesis than heterotrimers. Their fibrils have different mechanical properties. However, very little is known about their molecular interactions and fibrillogenesis in mixtures with normal heterotrimers. Here we studied the kinetics and thermodynamics of fibril formation in such mixtures by combining traditional approaches with 3D confocal imaging of fibrils, in which homo- and heterotrimers were labeled with different fluorescent colors. In a mixture, following a temperature jump from 4 to 32 degrees C, we observed a rapid increase in turbidity most likely caused by formation of homotrimer aggregates. The aggregates promoted nucleation of homotrimer fibrils that served as seeds for mixed and heterotrimer fibrils. The separation of colors in confocal images indicated segregation of homo- and heterotrimers at a subfibrillar level throughout the process. The fibril color patterns continued to change slowly after the fibrillogenesis appeared to be complete, due to dissociation and reassociation of the pepsin-treated homo- and heterotrimers, but this remixing did not significantly reduce the segregation even after several days. Independent homo- and heterotrimer solubility measurements in mixtures confirmed that the subfibrillar segregation was an equilibrium property of intermolecular interactions and not just a kinetic phenomenon. We argue that the subfibrillar segregation may exacerbate effects of a small fraction of alpha1(I) homotrimers on formation, properties, and remodeling of collagen fibers.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Han S,McBride DJ,Losert W,Leikin Sdoi
10.1016/j.jmb.2008.08.008subject
Has Abstractpub_date
2008-10-31 00:00:00pages
122-32issue
1eissn
0022-2836issn
1089-8638pii
S0022-2836(08)00988-1journal_volume
383pub_type
杂志文章abstract::Antibiotic chloramphenicol (CHL) binds with a moderate affinity at the peptidyl transferase center of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving properties of this inhibitor, we explored ribosome binding and inhibitory activity of a number of amin...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2018.01.016
更新日期:2018-03-16 00:00:00
abstract::Intrinsically disordered proteins (IDPs) lack stable tertiary structure under physiological conditions. The unique composition and complex dynamical behaviour of IDPs make them a challenge for structural biology and molecular evolution studies. Using NMR ensembles, we found that IDPs evolve under a strong site-specifi...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2020.166751
更新日期:2021-02-05 00:00:00
abstract::The negative regulatory domain (NRD) of the p53 tumor suppressor is intrinsically disordered. It contains several posttranslational modification (PTM) sites that are important for regulation of p53 activity. Calcium-dependent binding of dimeric S100B(ββ) to p53-NRD blocks access to these PTM sites and disrupts the p53...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2013.01.001
更新日期:2013-03-25 00:00:00
abstract::The structure of basic Winged Bean Agglutinin (WBAI) with two dimeric molecules complexed with methyl-alpha-D-galactopyranoside in the asymmetric unit, has been determined by the molecular replacement method and refined with 2.5 A X-ray intensity data. The polypeptide chain of each monomer has the characteristic legum...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1568
更新日期:1998-03-06 00:00:00
abstract::Restriction endonuclease BcnI cleaves duplex DNA containing the sequence CC/SGG (S stands for C or G, / designates a cleavage position) to generate staggered products with single nucleotide 5'-overhangs. Here, we show that BcnI functions as a monomer that interacts with its target DNA in 1:1 molar ratio and report cry...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.03.018
更新日期:2007-06-08 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::The basic leucine zipper domain of the yeast transcription factor GCN4 consists of a C-terminal leucine zipper and an N-terminal basic DNA-binding region that achieves a stable structure only after association with DNA. Backbone dynamics of a peptide encompassing the basic and leucine zipper bZip domain (residues 226-...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2429
更新日期:1999-02-05 00:00:00
abstract::Disulfide bonds play an important role in protein stability and function. Here, we describe a general procedure for generating disulfide-linked dimers and multimers of proteins of known crystal structures. An algorithm was developed to predict sites in a protein compatible with intermolecular disulfide formation with ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.07.033
更新日期:2007-10-05 00:00:00
abstract::UMP kinase (UMPK), the enzyme responsible for microbial UMP phosphorylation, plays a key role in pyrimidine nucleotide biosynthesis, regulating this process via feed-back control and via gene repression of carbamoyl phosphate synthetase (the first enzyme of the pyrimidine biosynthesis pathway). We present crystal stru...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.07.045
更新日期:2005-09-16 00:00:00
abstract::Carbohydrate-binding polypeptides, including carbohydrate-binding modules (CBMs) from polysaccharidases, and lectins, are widespread in nature. Whilst CBMs are classically considered distinct from lectins, in that they are found appended to polysaccharide-degrading enzymes, this distinction is blurring. The crystal st...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00152-9
更新日期:2003-03-28 00:00:00
abstract::A Xenopus laevis complementary DNA (cDNA) library prepared from messenger RNAs extracted from embryos has been screened for actin-coding sequences. Two cDNA clones corresponding to an alpha cardiac and an alpha skeletal muscle actin mRNA have been identified and characterized. From a genomic library, we have furthermo...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(86)90438-9
更新日期:1986-02-05 00:00:00
abstract::We characterize aspects of the conformation and dynamic state of RecA filaments when bound to dsDNA that are specifically linked to the presence of the second of the two bound DNA strands. Filaments bound to dsDNA exhibit a facile exchange between free and bound RecA monomers or oligomers in the filament interior that...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0200
更新日期:1996-04-12 00:00:00
abstract::Here, we report the molecular characterization of the human cytomegalovirus uracil DNA glycosylase (UNG) UL114. Purified UL114 was shown to be a DNA glycosylase, which removes uracil from double-stranded and single-stranded DNA. However, kinetic analysis has shown that viral UNG removed uracil more slowly compared wit...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.05.028
更新日期:2008-08-29 00:00:00
abstract::Collagens contain sequence- and conformation-dependent epitopes responsible for their digestion by collagenases at specific loci. A synthetic heterotrimer construct containing the collagenase cleavage site of collagen type I was found to mimic perfectly native collagen in terms of selectivity and mode of enzymatic deg...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/S0022-2836(02)00365-0
更新日期:2002-06-21 00:00:00
abstract::Despite the condensed nature of terminal sequences, the telomeres are transcribed into a group of noncoding RNAs, including the TElomeric Repeat-containing RNA (TERRA). Since the discovery of TERRA, its evolutionary conserved function has been confirmed, and its involvement in telomere length regulation, heterochromat...
journal_title:Journal of molecular biology
pub_type: 杂志文章,评审
doi:10.1016/j.jmb.2020.01.034
更新日期:2020-07-10 00:00:00
abstract::Crystals of a chymotrypsin inhibitor from Erythrina caffra seeds have been grown out of lithium sulfate, by the hanging drop method of vapor diffusion. The crystals belong to the rhombohedral space group R32, with a = 67.2 A and alpha = 99.4 degrees, and diffract to 3 A resolution. ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(90)90300-B
更新日期:1990-03-05 00:00:00
abstract::The structures of the two very closely related proteins, bovine gamma II- and gamma IVa-crystallin have been studied by means of near-ultra-violet linear dichroism spectroscopy on squeezed polyacrylamide gel systems. The crystallin spectra are discussed in terms of the spectra of the aromatic chromophores present in t...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(05)80069-5
更新日期:1990-11-05 00:00:00
abstract::Transcription of the Bacillus subtilis iol divergon is negatively regulated by a repressor encoded by iolR, which belongs to the DeoR family of bacterial regulators. Gel retardation analysis involving the IolR protein synthesized in Escherichia coli revealed that IolR bound specifically and independently to each of th...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.2398
更新日期:1999-01-22 00:00:00
abstract::RNA localization is an important means of post-transcriptional regulation of gene expression in many eukaryotic cell types. In neurons, select RNAs are delivered to postsynaptic dendritic microdomains, a mechanism that is considered a key underpinning in the administration of long-term synaptic plasticity. BC1 RNA is ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.11.090
更新日期:2006-03-10 00:00:00
abstract::The time-course of synthesis of long and short (abortive) transcripts by Escherichia coli RNA polymerase was investigated under single round conditions in vitro. The synthesis of long RNA initiated at the lambda PR (with an altered leader sequence) or at the lacUV5 promoter was completed within five minutes, but abort...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0100
更新日期:1996-03-01 00:00:00
abstract::The gene-3-protein (G3P) of filamentous phage is essential for their propagation. It consists of three domains. The CT domain anchors G3P in the phage coat, the N2 domain binds to the F pilus of Escherichia coli and thus initiates infection, and the N1 domain continues by interacting with the TolA receptor. Phage are ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00359-0
更新日期:2003-05-09 00:00:00
abstract::The sequence-specific assignment of resonances is considered to be a requirement for the determination of the three-dimensional (3D) structure of a protein in solution by nuclear magnetic resonance methods. The main source of structural information is the nuclear Overhauser effect spectroscopy (NOESY) spectrum, which ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(94)90042-6
更新日期:1994-11-04 00:00:00
abstract::In Escherichia coli, porin gene expression is regulated, in part, by the two-component regulatory system consisting of the two proteins EnvZ and OmpR. EnvZ is an integral inner membrane protein that is phosphorylated by cytoplasmic ATP on a histidine residue. EnvZ modulates the activity of OmpR by phosphorylation and ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1985
更新日期:1998-09-04 00:00:00
abstract::The structure and backbone dynamics of a double labelled (15N,13C) monomeric, 23.7 kD phosphoglycerate mutase (PGAM) from Schizosaccharomyces pombe have been investigated in solution using NMR spectroscopy. A set of 3125 NOE-derived distance restraints, 148 restraints representing inferred hydrogen bonds and 149 value...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.4390
更新日期:2001-02-16 00:00:00
abstract::Proteasomes, major proteolytic sites in eukaryotic cells, play an important part in major histocompatibility class I (MHC I) ligand generation and thus in the regulation of specific immune responses. Their cleavage specificity is of outstanding interest for this process. In order to generalize previously determined cl...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.3683
更新日期:2000-05-05 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::The yeast a1 and alpha 2 proteins are examples of homeodomain proteins that display cell-type-specific expression. They are co-expressed in only one type of cell, the a/alpha cell, where they repress the expression of a group of target genes. Using purified proteins, we demonstrate that a1 and alpha 2 form a highly sp...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1517
更新日期:1993-10-05 00:00:00
abstract::Progress in the structure determination of bacteriorhodopsin, the protein component of purple membrane from Halobacterium halobium has been limited by the lack of three-dimensional phase information between 6 and 3 A resolution. By analogy with X-ray methods, it is possible that heavy-atom labelling of the membrane cr...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/S0022-2836(05)80214-1
更新日期:1990-06-05 00:00:00
abstract::We showed earlier that the mutation of Leu99 to alanine in bacteriophage T4 lysozyme creates an internal cavity of volume approximately 150 A(3) that binds benzene and a variety of other ligands. As such, this cavity provides an excellent target to study protein-ligand interaction. Here, we use low-temperature crystal...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.10.086
更新日期:2009-01-16 00:00:00
abstract::The three-dimensional structure of ferric myoglobin from the mollusc Aplysia limacina has been refined at 2 X 0 A resolution. The crystallographic R factor, calculated at this stage, is 0 X 194. Despite its high content of apolar residues (both aromatic and aliphatic), Aplysia limacina myoglobin, which contains only o...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(85)90285-2
更新日期:1985-05-05 00:00:00