Search results for " folding"

Histone Code and Higher-Order Chromatin Folding: A Hypothesis

2016

AbstractHistone modifications alone or in combination are thought to modulate chromatin structure and function; a concept termed histone code. By combining evidence from several studies, we investigated if the histone code can play a role in higher-order folding of chromatin. Firstly using genomic data, we analyzed associations between histone modifications at the nucleosome level. We could dissect the composition of individual nucleosomes into five predicted clusters of histone modifications. Secondly, by assembling the raw reads of histone modifications at various length scales, we noticed that the histone mark relationships that exist at nucleosome level tend to be maintained at the high…

The GlpF residue Trp219 is part of an amino-acid cluster crucial for aquaglyceroporin oligomerization and function

2018

The vestibule loop regions of aquaglyceroporins are involved in accumulation of glycerol inside the channel pore. Even though most loop regions do not show high sequence similarity among aquaglyceroporins, loop E is highly conserved in aquaglyceroporins, but not in members of the homologous aquaporins. Specifically, a tryptophan residue is extremely conserved within this loop. We have investigated the role of this residue (Trp219) that deeply protrudes into the protein and potentially interacts with adjacent loops, using the E. coli aqualgyeroporin GlpF as a model. Replacement of Trp219 affects the activity of GlpF and impairs the stability of the tetrameric protein. Furthermore, we have id…

Local dynamic properties of the heme pocket in native and solvent-induced molten-globule-like states of cytochrome c

2002

We report the Soret absorption band, down to cryogenic temperature, of native and molten-globule-like state of horse heart cytochrome c. The band profile is analyzed in terms of vibronic coupling of the heme normal modes to the electronic transition in the framework of the Franck-Condon approximation. From the temperature dependence of the Gaussian broadening and of the peak position, we obtain information on the 'bath' of low frequency harmonic motions of the heme group within the heme pocket. The reported data indicate that, compared to the native state, the less rigid tertiary structure of the molten globule is reflected in a higher flexibility of the heme pocket and in greater conformat…

Probing a Polar Cluster in the Retinal Binding Pocket of Bacteriorhodopsin by a Chemical Design Approach

2012

Bacteriorhodopsin has a polar cluster of amino acids surrounding the retinal molecule, which is responsible for light harvesting to fuel proton pumping. From our previous studies, we have shown that threonine 90 is the pivotal amino acid in this polar cluster, both functionally and structurally. In an attempt to perform a phenotype rescue, we have chemically designed a retinal analogue molecule to compensate the drastic effects of the T90A mutation in bacteriorhodopsin. This analogue substitutes the methyl group at position C(13) of the retinal hydrocarbon chain by and ethyl group (20-methyl retinal). We have analyzed the effect of reconstituting the wild-type and the T90A mutant apoprotein…

Chaperones Involved in Hepatitis B Virus Morphogenesis

1999

Little is known about host cell factors necessary for hepatitis B virus (HBV) assembly which involves envelopment of cytosolic nucleocapsids by the S, M and L transmembrane viral envelope proteins and subsequent budding into intraluminal cisternae. Central to virogenesis is the L protein that mediates hepatocyte receptor binding and envelopment of capsids. To serve these topologically conflicting roles, L protein exhibits an unusual dual membrane topology, disposing its N-terminal preS domain inside and outside of the virion lipid envelope. The mixed topology is achieved by posttranslational preS translocation of about half of the L protein molecules across a post-endoplasmic reticulum memb…

Effect of a Rigid Sulfonamide Bond on Molecular Folding: A Case Study

2015

A disulfonamide compound with bulky aromatic side chains was prepared, and its properties as a potential building block for foldamers were evaluated. Two different solvate crystal forms of the compound were identified and compared to the structures of an analogous oligoamide and related disulfonamides. The disulfonamide is unfolded in one of the solvates, whereas in the other one, a loosely folded conformer stabilized by an intramolecular hydrogen bond is found. Density functional calculations indicated that the loosely folded conformer is slightly more stable than its unfolded isomer. The calculations also identified a third, more tightly folded and more extensively hydrogen bonded, confor…

Cryptogein affects expression of alpha3, alpha6 and beta1 20S proteasome subunits encoding genes in tobacco.

2001

Twelve a and b 20S proteasome subunits cDNAs showing 70–82% identity with the corresponding genes in Arabidopsis or rice, and features of eukaryotic proteasome subunits were cloned in tobacco. Only b1-tcI 7, a3 and a6, 20S proteasome subunits encoding genes were up-regulated by cryptogein, a proteinaceous elicitor of plant defence reactions. These results led to the hypothesis that the activation of b1-tcI 7, a3 and a6 could induce a specific proteolysis involved in the hypersensitive response and systemic acquired resistance monitored by cryptogein. In eukaryotes, the 26S proteasome is the central multicatalytic proteinase complex comprising two subcomplexes: the 20S core particle that per…

Molecular basis of filamin a-filGAP interaction and its impairment in congenital disorders associated with filamin a mutations

2008

Background Mutations in filamin A (FLNa), an essential cytoskeletal protein with multiple binding partners, cause developmental anomalies in humans. Methodology/Principal Findings We determined the structure of the 23rd Ig repeat of FLNa (IgFLNa23) that interacts with FilGAP, a Rac-specific GTPase-activating protein and regulator of cell polarity and movement, and the effect of the three disease-related mutations on this interaction. A combination of NMR structural analysis and in silico modeling revealed the structural interface details between the C and D β-strands of the IgFLNa23 and the C-terminal 32 residues of FilGAP. Mutagenesis of the predicted key interface residues confirmed the b…

Structural Studies of Self-Folding Cavitands

2000

Oxidation Enhances Human Serum Albumin Thermal Stability and Changes the Routes of Amyloid Fibril Formation

2014

Oxidative damages are linked to several aging-related diseases and are among the chemical pathways determining protein degradation. Specifically, interplay of oxidative stress and protein aggregation is recognized to have a link to the loss of cellular function in pathologies like Alzheimer's and Parkinson's diseases. Interaction between protein and reactive oxygen species may indeed induce small changes in protein structure and lead to the inhibition/modification of protein aggregation process, potentially determining the formation of species with different inherent toxicity. Understanding the temperate relationship between these events can be of utmost importance in unraveling the molecul…