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Hydrophobic Patches (hydrophobic + patch)

Distribution by Scientific Domains

Chemistry	50%
Life Sciences	42%

Distribution within Chemistry

Biochemistry	42%

Selected Abstracts

The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8

GENES TO CELLS, Issue 7 2004
Kenji Sugawara
Microtubule-associated protein light chain 3 (LC3), a mammalian homologue of yeast Atg8, plays an essential role in autophagy, which is involved in the bulk degradation of cytoplasmic components by the lysosomal system. Here, we report the crystal structure of LC3 at 2.05 Å resolution with an R-factor of 21.8% and a free R-factor of 24.9%. The structure of LC3, which is similar to those of Golgi-associated ATPase enhancer of 16 kDa (GATE-16) and GABAA receptor-associated protein (GABARAP), contains a ubiquitin core with two , helices, ,1 and ,2, attached at its N-terminus. Some common and distinct features are observed among these proteins, including the conservation of residues required to form an interaction among ,1, ,2 and the ubiquitin core. However, the electrostatic potential surfaces of these helices differ, implicating particular roles to select specific binding partners. Hydrophobic patches on the ubiquitin core of LC3, GABARAP and GATE-16 are well conserved and are similar to the E1 binding surface of ubiquitin and NEDD8. Therefore, we propose that the hydrophobic patch is a binding surface for mammalian Atg7 similar to a ubiquitin-like conjugation system. We also propose the functional implications of the ubiquitin fold as a recognition module of target proteins. [source]

Molecular mechanism of ubiquitin recognition by GGA3 GAT domain

GENES TO CELLS, Issue 7 2005
Masato Kawasaki
GGA (Golgi-localizing, ,-adaptin ear domain homology, ARF-binding) proteins, which constitute a family of clathrin coat adaptor proteins, have recently been shown to be involved in the ubiquitin-dependent sorting of receptors, through the interaction between the C-terminal three-helix-bundle of the GAT (GGA and Tom1) domain (C-GAT) and ubiquitin. We report here the crystal structure of human GGA3 C-GAT in complex with ubiquitin. A hydrophobic patch on C-GAT helices ,1 and ,2 forms a binding site for the hydrophobic Ile44 surface of ubiquitin. Two distinct orientations of ubiquitin Arg42 determine the shape and the charge distribution of ubiquitin Ile44 surface, leading to two different binding modes. Biochemical and NMR data strongly suggest another hydrophobic binding site on C-GAT helices ,2 and ,3, opposite to the first binding site, also binds ubiquitin although weakly. The double-sided ubiquitin binding provides the GAT domain with higher efficiency in recognizing ubiquitinated receptors for lysosomal receptor degradation. [source]

The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8

Transient complexes of redox proteins: structural and dynamic details from NMR studies

JOURNAL OF MOLECULAR RECOGNITION, Issue 6 2004
Miguel Prudêncio
Abstract Redox proteins participate in many metabolic routes, in particular those related to energy conversion. Protein,protein complexes of redox proteins are characterized by a weak affinity and a short lifetime. Two-dimensional NMR spectroscopy has been applied to many redox protein complexes, providing a wealth of information about the process of complex formation, the nature of the interface and the dynamic properties of the complex. These studies have shown that some complexes are non-specific and exist as a dynamic ensemble of orientations while in other complexes the proteins assume a single orientation. The binding interface in these complexes consists of a small hydrophobic patch for specificity, surrounded by polar, uncharged residues that may enhance dissociation, and, in most complexes, a ring or patch of charged residues that enhances the association by electrostatic interactions. The entry and exit port of the electrons is located within the hydrophobic interaction site, ensuring rapid electron transfer from one redox centre to the next. Copyright © 2004 John Wiley & Sons, Ltd. [source]

The geometry and motion of nematode sperm cells

CYTOSKELETON, Issue 6 2009
Evgeny Demekhin
Abstract The nematode sperm cell crawls by recycling major sperm protein (MSP) from dimers into subfilaments, filaments, and filament complexes, as a result of thermal writhing in the presence of hydrophobic patches. Polymerization near leading edges of the cell intercolates MSP dimers onto the tips of growing filament complexes, forcing them against the cell boundary, and extending the cytoskeleton in the direction of motion. Strong adhesive forces attach the cell to the substrate in the forward part of the lamellipod, while depolymerization in the rearward part of the cell breaks down the cytoskeleton, contracting the lamellipod and pulling the cell body forward. The movement of these cells, then, is caused by coordinated protrusive, adhesive and contractile forces, spatially separated across the lamellipod. This paper considers a phenomenological model that tracks discrete elements of the cytoskeleton in curvilinear coordinates. The pseudo-two dimensional model primarily considers protrusion and rotation of the cell, along with the evolution of the cell boundary. General assumptions are that pH levels within the lamellipod regulate protrusion, contraction and adhesion, and that growth of the cytoskeleton, over time, is perpendicular to the evolving cell boundary. The model follows the growth and contraction of a discrete number of MSP fiber complexes, since they appear to be the principle contributors for force generation in cell boundary protrusion and contraction, and the backbone for the dynamic geometry and motion. Cell Motil. Cytoskeleton 2009. © 2009 Wiley-Liss, Inc. [source]

The histidine-phosphocarrier protein of Streptomyces coelicolor folds by a partially folded species at low pH

FEBS JOURNAL, Issue 10 2003
Gregorio Fernández-Ballester
The folding of a 93-residue protein, the histidine-phosphocarrier protein of Streptomyces coelicolor, HPr, has been studied using several biophysical techniques, namely fluorescence, 8-anilinonaphthalene-1-sulfate binding, circular dichroism, Fourier transform infrared spectroscopy, gel filtration chromatography and differential scanning calorimetry. The chemical-denaturation behaviour of HPr, followed by fluorescence, CD and gel filtration, at pH 7.5 and 25 °C, is described as a two-state process, which does not involve the accumulation of thermodynamically stable intermediates. Its conformational stability under those conditions is ,G = 4.0 ± 0.2 kcal·mol,1 (1 kcal = 4.18 kJ), which makes the HPr from S. coelicolor the most unstable member of the HPr family described so far. The stability of the protein does not change significantly from pH 7,9, as concluded from the differential scanning calorimetry and thermal CD experiments. Conformational studies at low pH (pH 2.5,4) suggest that, in the absence of cosmotropic agents, HPr does not unfold completely; rather, it accumulates partially folded species. The transition from those species to other states with native-like secondary and tertiary structure, occurs with a pKa = 3.3 ± 0.3, as measured by the averaged measurements obtained by CD and fluorescence. However, this transition does not agree either with: (a) that measured by burial of hydrophobic patches (8-anilinonaphthalene-1-sulfate binding experiments); or (b) that measured by acquisition of native-like compactness (gel-filtration studies). It seems that acquisition of native-like features occurs in a wide pH range and it cannot be ascribed to a unique side-chain titration. These series of intermediates have not been reported previously in any member of the HPr family. [source]

Peau sèche-rêche et "Hydratation".

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 4 2004
Concept de la capture de l'eau organisée comme de la glace
Synopsis About sixty years ago Frank and Evans showed, by entropy measurements, that when a "non-polar molecule dissolves in water it modifies the water structure in the direction of greater ,cristallinity', the water builds a microscopic iceberg around it" Now, we propose the "concept of ice-like-water capture": a lowering of organized ice-like water promotes aggregation (loss of solubility) of the filaggrin/keratin1/keratin10 associations through their hydrophobic patches. The capture of ice-like water may be performed by the glucoceramides-rich bilayers in stratum granulosum. Probably, the same process aggregates the proteins of corneocytes envelope as well as corneodesmosomes proteins. According to the "concept of ice-like-water capture", to regulate the keratinization, it is not total water that must be added to the stratum corneum, but ice-like water that must be removed from stratum granulosum. Both petrolatum (lipophilic ingredient) and glycerol (hydrophilic ingredient) would capture the ice-like water, most probably after combination with the lipid bilayers of stratum corneum. Moisturizing cream, when organized in secondary droplets is likely to perform the same action. Measurements by near-infrared reflectance spectroscopy of the skin show that petrolatum; glycerol and/or moisturizing cream enhance the quantity of bulk water (1890,1897 nm band). As the ice-like water is the complement of bulk water, the enhanced bulk water let presume an ice-like water lessening. Some desynchronization (late or forward) of the keratinization/differentiation which confer the somatosensory problems associated with "dry and flaky skin" may be linked to an excess or lack of ice-like. For instance, the winter xerosis, very common by chilling weather, could be explained by an increase of ice-like water driven by the fall of the temperature. Résumé En s'appuyant: 1°-sur d'anciens travaux de thermodynamique montrant, d'une part que les molécules d'eau autour des zones apolaires en solution dans l'eau s'organise selon une structure d'eau-comme-de-la-glace, d'autre part qu'en l'absence de cette eau-comme-de-la-glace les molécules de protéines s'agrègent par leurs zones hydrophobes; 2°-sur des travaux récents utilisant la spectroscopie de l'infrarouge proche; technique qui permet de mesurer la quantité d'eau-en-vrac, forme que prend l'eau-comme-de-la-glace après sa fusion lors de l"établissement de liaisons/interactions hydrophobes; nous proposons le "concept de la capture de l"eau-comme-de-la-glace" selon lequel : 1° la différenciation des kératinocytes, qui se traduit à la fois par l'agrégation des trios filaggrine/K1/K10 (ainsi que notamment la formation de l'enveloppe des cornéocytes et des cornéodesmosomes) est promue par une baisse de la teneur en eau organisée dans le stratum granulosum. La captation de l'eau-comme-de-la-glace pourrait être assurée in situ par la structure lipidique riche en glucocéramides dont l'apparition dans le stratum granulosum est contemporaine du début de la baisse de la teneur en eau; 2° contrairement à la "tradition", la peau sèche-rêche n'est pas améliorée par une augmentation de l'hydratation du stratum corneum mais par la capture d'eau-comme-de-la-glace dans le stratum granulosum. 3° le glycérol, la Vaseline et les crèmes "hydratantes" peuvent concourir à cette capture d'eau-comme-de-la-glace, vraisemblablement après s"être combinés aux bicouches céramidiques du stratum corneum, et ainsi agir depuis ce stratum sur le stratum granulosum. 4°-la baisse hivernale de la température provoque une baisse de la quantité d'eau organisée et confère une aggravation de la peau sèche-rêche. 5°-une désynchronisation de la synthèse ou une modification de la structure et/ou de la composition des bicouches glucocéramidiques du stratum granulosum pourraient être à l'origine de certains types de peau sèche-rêche. [source]

Chaperone-like activity and hydrophobicity of ,-crystallin

IUBMB LIFE, Issue 11 2006
G. Bhanuprakash Reddy
Abstract ,-Crystallin, a prominent member of small heat shock protein (sHsp) family and a major structural protein of the eye lens is a large polydisperse oligomer of two isoforms, ,A- and ,B-crystallins. Numerous studies have demonstrated that ,-crystallin functions like a molecular chaperone in preventing the aggregation of various proteins under a wide range of stress conditions. The molecular chaperone function of ,-crystallin is thus considered to be vital in the maintenance of lens transparency and in cataract prevention. ,-Crystallin selectively interacts with non-native proteins thereby preventing them from aggregation and helps maintain them in a folding competent state. It has been proposed and generally accepted that ,-crystallin suppresses the aggregation of other proteins through the interaction between hydrophobic patches on its surface and exposed hydrophobic sites of partially unfolded substrate protein. However, a quantifiable relationship between hydrophobicity and chaperone-like activity remains a matter to be concerned about. On an attentive review of studies on ,-crystallin chaperone-like activity, particularly the studies that have direct or indirect implications to hydrophobicity and chaperone-like activity, we found several instances wherein the correlation between hydrophobicity and its chaperone-like activity is paradoxical. We thus attempted to provide an overview on the role of hydrophobicity in chaperone-like activity of ,-crystallin, the kind of evaluation done for the first time. iubmb Life, 58: 632 - 641, 2006 [source]

Structure-based mutagenesis of SigE verifies the importance of hydrophobic and electrostatic residues in type III chaperone function

MOLECULAR MICROBIOLOGY, Issue 4 2006
Leigh A. Knodler
Summary Despite sharing little sequence identity, most type III chaperones display a similar homodimeric structure characterized by negative charges distributed broadly over their entire surface, interspersed with hydrophobic patches. Here we have used SigE from Salmonella as a model for class IA type III chaperones to investigate the role of these surface-exposed residues in chaperone function. SigE is essential for the stability, secretion and translocation of its cognate effector, SopB (SigD). We analysed the effect of mutating nine conserved hydrophobic and electronegative surface-exposed amino acids of SigE on SopB binding, stability, secretion and translocation. Six of these mutations affected some aspect of SigE function (Leu14, Asp20, Leu22, Leu23, Ile25 and Asp51) and three were without effect (Leu54, Glu92 and Glu99). Our results highlight that both hydrophobic and electronegative surfaces are required for the function of SigE and provide an important basis for the prediction of side-chain requirements for other chaperone,effector pairs. [source]

Structures of and interactions between domains of trigger factor from Thermotoga maritima

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2007
Erik Martinez-Hackert
Trigger factor (TF) is a eubacterial chaperone that associates with ribosomes at the peptide-exit tunnel and also occurs in excess free in the cytosol. TF is a three-domain protein that appears to exist in a dynamic equilibrium of oligomerization states and interdomain conformations. X-ray crystallography and chemical cross-linking were used to study the roles of the N- and C-terminal domains of Thermotoga maritima TF in TF oligomerization and chaperone activity. The structural conservation of both the N- and C-terminal TF domains was unambiguously established. The biochemical and crystallographic data reveal a tendency for these domains to partake in diverse and apparently nonspecific protein,protein interactions. It is found that the T. maritima and Escherichia coli TF surfaces lack evident exposed hydrophobic patches. Taken together, these data suggest that TF chaperones could interact with nascent proteins via hydrophilic surfaces. [source]

A new crystal form of Lys48-linked diubiquitin

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2010
Jean-François Trempe
Lys48-linked polyubiquitin chains are recognized by the proteasome as a tag for the degradation of the attached substrates. Here, a new crystal form of Lys48-linked diubiquitin (Ub2) was obtained and the crystal structure was refined to 1.6,Å resolution. The structure reveals an ordered isopeptide bond in a trans configuration. All three molecules in the asymmetric unit were in the same closed conformation, in which the hydrophobic patches of both the distal and the proximal moieties interact with each other. Despite the different crystallization conditions and different crystal packing, the new crystal structure of Ub2 is similar to the previously published structure of diubiquitin, but differences are observed in the conformation of the flexible isopeptide linkage. [source]

Fibrillation of ,-lactalbumin: Effect of crocin and safranal, two natural small molecules from Crocus sativus,

BIOPOLYMERS, Issue 10 2010
Mohammad-Bagher Ebrahim-Habibi
Abstract Formation of toxic amyloid structures is believed to be associated with various late-onset neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The fact that many proteins in addition to those that are associated with clinical conditions have the potential to form amyloid fibrils in vitro provides opportunities for studying the fundamentals of protein aggregation and amyloid formation in model systems. Accordingly, considerable interest and effort has been directed toward developing small molecules to inhibit the formation of fibrillar assemblies and their associated toxicities. In the present study, we investigated the inhibitory effect of crocin and safranal, two principal components of saffron, on fibrillation of apo-,-lactalbumin (a-,-LA), used as a model protein, under amyloidogenic conditions. In the absence of any ligand, formation of soluble oligomers became evident after 18 h of incubation, followed by subsequent appearance of mature fibrils. Upon incubation with crocin or safranal, while transition phase to monomeric beta structures was not significantly affected, formation of soluble oligomers and following fibrillar assemblies were inhibited. While both safranal and crocin had the ability to bind to hydrophobic patches provided in the intermediate structures, and thereby inhibit protein aggregation, crocin was found more effective, possibly due to its simultaneous hydrophobic and hydrophilic character. Cell viability assay indicated that crocin could diminish toxicity while safranal act in reverse order. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 854,865, 2010. [source]

Low versus high molecular weight poly(ethylene glycol)-induced states of stem bromelain at low pH: Stabilization of molten globule and unfolded states

BIOPOLYMERS, Issue 5 2006
Basir Ahmad
Abstract The effect of low, medium, and high molecular weight poly(ethylene glycol) (e.g., PEG-400, -6000, and -20,000) on the structure of the acid unfolded state of unmodified stem bromelain (SB) obtained at pH 2.0 has been studied by various spectroscopic methods. The conformation of stem bromelain at pH 2.0 exhibits substantial loss of secondary structure and almost complete loss of native tertiary contacts and has been termed the acid unfolded state (AU). Addition of PEG-400 to AU led to an increase in the mean residue ellipticity (MRE) value at 222 nm, indicating formation of ,-helical structure. On the other hand, PEG-6000 and 20,000 led to a decrease in the MRE value at 222 nm, indicating unfolding of the AU state. Interestingly, at 70% (w/v) PEG-400 and 40% (w/v) PEG-20,000, MRE values at 222 nm almost approach the native state at pH 7.0 and the unfolded state (6 M GnHCl) of stem bromelain, respectively. The probes for tertiary structure showed formation of nonnative tertiary contacts in the presence of 70% (w/v) PEG-400, while 40% (w/v) PEG-6000 and 20,000 were found to stabilize the unfolded state of SB. An increase in binding of 1-anilino 8-naphthalene sulfonic acid and a decrease in fractional accessibility of tryptophan residues (fa) compared to AU in the presence of 70% PEG-400 indicate that the PEG-400,induced state has a significant amount of exposed hydrophobic patches and is more compact than AU. The results imply that the PEG-400,induced state has characteristics of molten globule, and higher molecular weight PEGs led to the unfolding of the AU state. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 350,359, 2006 This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]

Structure of the ThDP-dependent enzyme benzaldehyde lyase refined to 1.65,Å resolution

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 7 2007
Andy Maraite
Benzaldehyde lyase (BAL; EC 4.1.2.38) is a thiamine diphosphate (ThDP) dependent enzyme that catalyses the enantioselective carboligation of two molecules of benzaldehyde to form (R)-benzoin. BAL has hence aroused interest for its potential in the industrial synthesis of optically active benzoins and derivatives. The structure of BAL was previously solved to a resolution of 2.6,Å using MAD experiments on a selenomethionine derivative [Mosbacher et al. (2005), FEBS J.272, 6067,6076]. In this communication of parallel studies, BAL was crystallized in an alternative space group (P212121) and its structure refined to a resolution of 1.65,Å, allowing detailed observation of the water structure, active-site interactions with ThDP and also the electron density for the co-solvent 2-methyl-2,4-pentanediol (MPD) at hydrophobic patches of the enzyme surface. [source]