Disease relevance of Protein Conformation

• Our studies indicate that HSP70 or related molecular chaperones may provide a means of treating these and other neurodegenerative diseases associated with abnormal protein conformation and toxicity [1].
• These findings suggest the possibility that the conversion of the cellular isoform of PrP to the scrapie isoform of PrP involves the transition of one or more putative PrP alpha-helices into beta-sheets and that prion diseases are disorders of protein conformation [2].
• However, introduction of individual substitution mutations in this region did not impair Vpr nuclear localization and virion incorporation, suggesting that this region is necessary for the stability and/or optimal protein conformation relevant to these Vpr functions [3].
• The naturally occurring mutation L141R (also associated with coronary heart disease) that is located in this segment does not change the protein conformation but leads to a reduced stability and a decreased rate of association with DMPC liposomes that may relate to the observed altered functions of this mutant [4].
• On the contrary, studies with plasma or albumin have highlighted the importance of protein conformation in dethiolation processes and have clarified the reason why homocysteine (thiol with potential toxicity) is preferentially bound to albumin as protein-thiol mixed disulfide with respect to other NPSH [5].

High impact information on Protein Conformation

• These are propagated and amplified across the plug, eventually resulting in substantially different protein conformations at the periplasmic face [6].
• Optical properties of single elastin fibres indicate random protein conformation [7].
• The coupling between protein conformation and nucleotide hydrolysis in Fe-protein exhibits general similarities to the H-Ras p21 and recA proteins that have been recently characterized structurally [8].
• This model predicts that C/EBP must undertake significant changes in protein conformation as it binds and releases DNA [9].
• The data agree with the concept that water retention in cells is due to multilayer adsorption on proteins and that the maintenance of the normal state of water relies on the presence of adenosine triphosphate as a cardinal adsorbent, controlling the protein conformations [10].

Biological context of Protein Conformation

• These results confirm that LHC proteins exist in multiple conformations, an idea suggested by previous spectroscopic measurements (Moya et al., 2001), and imply that the switch between the different LHC protein conformations is activated by the binding of zeaxanthin to the allosteric site L2 [11].
• One amino acid substitution of proline in GRO alpha by leucine in GRO beta and GRO gamma leads to a large predicted change in protein conformation [12].
• We found that although both forms of p53 induced apoptosis following expression of the wild-type protein conformation, the kinetics were different [13].
• Phosphorylations of two types are discernible; most phosphorylations do not significantly affect the mobility of the protein in sodium dodecyl sulfate-containing gels but one does, probably reflecting a phosphorylation-induced alteration in protein conformation [14].
• The effect of competitive inhibition of the reaction by 2,3-diphosphoglyceric acid, the dependence of the reaction rate on the protein conformation, hemoglobin mutants, and the diethylpyrocarbonate are consistent with the assignment of the active site [15].

Anatomical context of Protein Conformation

• These results are consistent with a change in the protein conformation of MPP154A at the nonpermissive temperature, which gives rise to a protein that fails to modify the molecular size-exclusion limits of plasmodesmata to the same extent as wild-type MP [16].
• To determine the protein conformation of these abnormal fibers, we have obtained x-ray diffraction patterns from unfixed human brain fractions highly enriched in PHF and from purified amyloid cores isolated from senile plaques [17].
• Thus the significance of myristoylation for Nef function may be in influencing protein conformation, although these data could be explained by a transient and dynamic interaction between myristoylated Nef and the plasma membrane [18].
• Following transfections into COS cells, phosphorylation, TAg binding and protein conformation were evaluated [19].
• A model is proposed herein describing the probable role of Smf1 protein conformation in directing its movement to the vacuole versus cell surface in response to changes in metal ion availability [20].

Associations of Protein Conformation with chemical compounds

• Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation [21].
• Carbohydrate chains on a glycoprotein are important not only for protein conformation, transport and stability, but also for cell-cell and cell-matrix interactions [22].
• The binding of patients' IgE to the recombinant allergen depended on the native protein conformation and protein-bound Ca2+ [23].
• Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation [24].
• Protein conformation changes resulting from a change in the ionization state of amino acids of different pKa values could change the tryptophan-retinal (or tryptophan-tyrosinate) coupling and thus the quenching efficiency [25].

Gene context of Protein Conformation

• This p53 function is abrogated by p53 gene mutations leading to alteration of protein conformation [26].
• Functionality of human thymine DNA glycosylase requires SUMO-regulated changes in protein conformation [27].
• Crystal structures show minimal changes in protein conformation but substantial changes in local surface topography at the site of the mutation, which is located in the region of NBD1 believed to interact with the first membrane spanning domain of CFTR [28].
• A temperature decrease to 32 degrees C causes conversion to a protein conformation that is capable of inducing expression of MDM2, leading to reduction of reactivated p53 levels by negative feedback [26].
• Furthermore, our data suggest that the DBD of the VDR adopts different protein conformations when contacting distinct VDREs [29].

Analytical, diagnostic and therapeutic context of Protein Conformation

• To investigate the molecular mechanisms of thermal inactivation and cholesterol protection, the responses of the physical state of the lipid and protein conformation to hyperthermic sensitizers and protector were monitored using fluorescent and spin label probes and circular dichroism, respectively [30].
• Isothermal titration calorimetry was used to determine the enthalpy for the calcium-dependent protein conformation change and subsequent interaction of blood clotting factor X and prothrombin with phospholipid vesicles [31].
• To address this issue, we combined apoD and Abeta immunohistochemistry with ThioS/X-34 staining of the beta-pleated sheet protein conformation in temporal cortex from 36 AD patients and 12 non-demented controls [32].
• This required monitoring the brushite transformation and surface adsorbed protein conformation simultaneously which can be realized using FTIR/ATR [33].
• Changes in the protein conformation of human spermatozoal membranes after treatment with cyclic adenosine 3':5'-monophosphate and human follicular fluid [34].

References