ASAView: Database and tool for solvent accessibility representation in proteins

Ahmad, Shandar; Gromiha, M. Michael; Fawareh, Hamed; Sarai, Akinori

doi:10.1186/1471-2105-5-51

Cited by 253 publications

(105 citation statements)

References 26 publications

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“…Relative solvent accessible surface area of core-buried residues in the crystal structures of nAChR-␣1 ECD (PDB code 2QC1), GLIC (3EAM), Lymnaea stagnalis Ls-AChBP (PDB code 1UV6), and Aplysia californica Ac-AChBP (PDB code 2BYN) was calculated with ASAView (36).…”

Section: Methodsmentioning

confidence: 99%

Packing of the Extracellular Domain Hydrophobic Core Has Evolved to Facilitate Pentameric Ligand-gated Ion Channel Function

Dellisanti

Hanson

Chen

et al. 2011

Journal of Biological Chemistry

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Protein function depends on conformational flexibility and folding stability. Loose packing of hydrophobic cores is not infrequent in proteins, as the enhanced flexibility likely contributes to their biological function. Here, using experimental and computational approaches, we show that eukaryotic pentameric ligand-gated ion channels are characterized by loose packing of their extracellular domain ␤-sandwich cores, and that loose packing contributes to their ability to rapidly switch from closed to open channel states in the presence of ligand. Functional analyses of GABA A receptors show that increasing the ␤-core packing disrupted GABA-mediated currents, with impaired GABA efficacy and slowed GABA current activation and desensitization. We propose that loose packing of the hydrophobic ␤-core developed as an evolutionary strategy aimed to facilitate the allosteric mechanisms of eukaryotic pentameric ligand-gated ion channels.Proteins are conformationally dynamic and require thermodynamic stability and structural flexibility to function (1-5). Stability and flexibility are interdependent, with higher stability increasing structural rigidity, which in many cases reduces protein activity (6). Proteins are only marginally stable, with ⌬G folding values mostly between Ϫ3 and Ϫ15 kcal/ mol (7). Trade-offs between thermodynamic stability and conformational flexibility are observed during protein evolution, with novel or specialized functions often acquired at the expense of stability (1,2,8,9). New-function mutations, however, rarely involve active site residues (10, 11) but occur with high frequencies in hydrophobic cores (12). Core mutations, although, are highly demanding in terms of stability, because a well packed hydrophobic core is the major factor that drives protein folding and maintains a stably folded structure through entropic ("hydrophobic effect") and enthalpic (van der Waals interactions) forces (13-16).Protein cores are normally packed with amino acid residues with bulky hydrophobic side chains that efficiently fill the space (17, 18). Core mutations tend to loosen the packing and create "defects" (empty or water-filled cavities) that decrease thermodynamic stability up to several kcal/moles (3, 19 -21). Numerous proteins (e.g. p53 (22), serpins (23), and hemagglutinin (24, 25)) have evolved localized core packing defects that enhance their biological activity at the cost of their stability.Recently, the crystal structure of the extracellular domain of the nicotinic acetylcholine receptor (nAChR) 3 ␣1 subunit revealed a hydrophilic water-filled cavity buried in the hydrophobic core of the protein and it was hypothesized that loose core packing is important for nAChR activity (26). nAChRs are members of the pentameric ligand-gated ion channel (pLGIC) superfamily, which includes ␥-aminobutyric acid (GABA A Rs), serotonin (5-HT 3 Rs), and glycine (GlyRs) receptors. For these receptors, binding of neurotransmitter to the extracellular ligand-binding domain triggers rapid structural rearrangements (in the ...

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Section: Methodsmentioning

confidence: 99%

Packing of the Extracellular Domain Hydrophobic Core Has Evolved to Facilitate Pentameric Ligand-gated Ion Channel Function

Dellisanti

Hanson

Chen

et al. 2011

Journal of Biological Chemistry

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“…The arrows point to differences in surface charges between the 2 proteins. Image resolved using ASAview [214] .…”

Section: The Immune Barriermentioning

confidence: 99%

Survival of encapsulated islets: More than a membrane story

Barkai¹,

Rotem²,

Vos³

2016

WJT

116

109

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“…As no crystal structure of BSA has been deposited in the Protein Data Bank, a homology model was obtained from the SWISS-MODEL Repository (17) based on the crystal structure of human serum albumin as a template (Protein Data Bank code 1N5U). To detect possible correlations between the degree of biotinylation, the local environment of lysine residues, and the solvent-accessible surface (18), their involvement in hydrogen bonding, the hydrogen bond energy, and the local electrostatic potential were studied. The latter was computed and visualized using the MOLCAD module of SYBYL 7.1 (19); hydrogen bond energies were calculated using the MAB force field implemented in MOLOC (20).…”

Section: Methodsmentioning

confidence: 99%

Use of Biotin Derivatives to Probe Conformational Changes in Proteins

Azimzadeh

Hillebrecht

Linne

et al. 2007

Journal of Biological Chemistry

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Sulfosuccinimidyl-6-(biotinamido) hexanoate and derivatives thereof covalently bind to the ⑀-amino group of lysine residues. Our observation that access of the biotin derivative to specific lysine residues depends on conformational properties of the entire polypeptide chain prompted us to investigate whether differential biotinylation patterns of a protein can be used as indicators for conformational changes. Bovine serum albumin is a soluble protein with characteristic unfolding kinetics upon exposure to high temperature. First, we show that biotinylation patterns of proteins are highly reproducible. Second, we demonstrate by mass spectrometry and tandem mass spectrometry that unfolding of the protein correlates with the accessibility of the biotin derivative to specific lysine residues. We have applied this experimental strategy to the analysis of a cell-surface protein, viz. the human band 3 anion exchanger of erythrocytes infected with the malaria parasite Plasmodium falciparum. The biotinylation of proteins is a commonly used tool for the affinity purification of proteins (1). It takes advantage of the highly specific interaction between biotin and avidin or its bacterial homolog, streptavidin. Protein biotinylation utilizes biotin derivatives containing an active ester group that reacts with primary amines of proteins, particularly with the N terminus and the ⑀-amino group of lysine residues. A novel amide bond is thereby formed, and the biotin moiety is covalently attached to the respective amino group, often separated by a spacer of defined size. The biotin derivative sulfosuccinimidyl-6-(biotinamido) hexanoate (sulfo-NHS-LC-biotin) 3 is a hydrophilic reagent that is excluded from most cells and is therefore used for the biotinylation and subsequent affinity purification of cellsurface proteins.Recently, we used sulfo-NHS-LC-biotin to label proteins exposed on the surface of human red blood cells infected with the malaria parasite Plasmodium falciparum (iRBC) (2). In contrast to the non-infected erythrocyte (RBC), the plasma membrane of the infected erythrocyte was permeable for this biotin derivative (2). Uptake of the compound occurs through the socalled novel permeability pathways, which are parasite-induced and have a broad specificity with a preference for anions (3-6). Biotinylation of internal proteins can be minimized if the reaction occurs in the presence of novel permeability pathway inhibitors such as furosemide. The proteins that constitute the novel permeability pathway are still unknown. The band 3 anion exchanger AE1 is the most abundant anion transporter in RBC (7). The reactivity of an epitope-specific monoclonal antibody with band 3, which differs between infected and noninfected erythrocytes, has been interpreted as a conformational change in the protein in at least one of the extracellular domains (8). Although band 3 itself does not appear to be the actual channel protein mediating the novel permeability pathway (5), its conformational change as a consequence of the infection may nev...

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ASAView: Database and tool for solvent accessibility representation in proteins

Cited by 253 publications

References 26 publications

Packing of the Extracellular Domain Hydrophobic Core Has Evolved to Facilitate Pentameric Ligand-gated Ion Channel Function

Packing of the Extracellular Domain Hydrophobic Core Has Evolved to Facilitate Pentameric Ligand-gated Ion Channel Function

Survival of encapsulated islets: More than a membrane story

Use of Biotin Derivatives to Probe Conformational Changes in Proteins

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