ArticleBMC biology2009
Evidence for the adaptation of protein pH-dependence to subcellular pH.
Article in BMC biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Computation suggests that the cell adhesion sub-proteome is enriched for sites of pH-dependence and charge burial.PloS one · 2025Article
- Effects of Phosphorylation on Protein Backbone Dynamics and Conformational Preferences.Journal of chemical theory and computation · 2024Article
- Leveraging genomic information to predict environmental preferences of bacteria.The ISME journal · 2024Review
- The pH Robustness of Bacterial Sensing.mBio · 2022Article
- The Physical Basis for pH Sensitivity in Biomolecular Structure and Function, With Application to the Spike Protein of SARS-CoV-2.Frontiers in molecular biosciences · 2022Review
- pHLARE: a new biosensor reveals decreased lysosome pH in cancer cells.Molecular biology of the cell · 2021Article
- Protein pI and Intracellular Localization.Frontiers in molecular biosciences · 2021Review
- Localization-specific distributions of protein pI in human proteome are governed by local pH and membrane charge.BMC molecular and cell biology · 2019Article
- Surface patches on recombinant erythropoietin predict protein solubility: engineering proteins to minimise aggregation.BMC biotechnology · 2019Article
- Web-based display of protein surface and pH-dependent properties for assessing the developability of biotherapeutics.Scientific reports · 2019Article
- Marginal protein stability drives subcellular proteome isoelectric point.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Light Control of Protein Solubility Through Isoelectric Point Modulation.Journal of the American Chemical Society · 2017Article
- Stability-Diversity Tradeoffs Impose Fundamental Constraints on Selection of Synthetic Human VFrontiers in immunology · 2017Article
- Isoelectric point region pI≈7.4 as a treasure island of abnormal proteoforms in blood.Discoveries (Craiova, Romania) · 2016Article
- Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.Journal of the American Society of Nephrology : JASN · 2015Article
- Engineering an Anti-Transferrin Receptor ScFv for pH-Sensitive Binding Leads to Increased Intracellular Accumulation.PloS one · 2015Article
- Energetic Calculations to Decipher pH-Dependent Oligomerization and Domain Swapping of Proteins.PloS one · 2015Article
- Soluble expression of proteins correlates with a lack of positively-charged surface.Scientific reports · 2013Article
- Molecular mechanisms of disease-causing missense mutations.Journal of molecular biology · 2013Review
- Considering protonation as a posttranslational modification regulating protein structure and function.Annual review of biophysics · 2013Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
backgroundThe availability of genome sequences, and inferred protein coding genes, has led to several proteome-wide studies of isoelectric points. Generally, isoelectric points are distributed following variations on a biomodal theme that originates from the predominant acid and base amino acid sidechain pKas. The relative populations of the peaks in such distributions may correlate with environment, either for a whole organism or for subcellular compartments. There is also a tendency for isoelectric points averaged over a subcellular location to not coincide with the local pH, which could be related to solubility. We now calculate the correlation of other pH-dependent properties, calculated from 3D structure, with subcellular pH.
resultsFor proteins with known structure and subcellular annotation, the predicted pH at which a protein is most stable, averaged over a location, gives a significantly better correlation with subcellular pH than does isoelectric point. This observation relates to the cumulative properties of proteins, since maximal stability for individual proteins follows the bimodal isoelectric point distribution. Histidine residue location underlies the correlation, a conclusion that is tested against a background of proteins randomised with respect to this feature, and for which the observed correlation drops substantially.
conclusionThere exists a constraint on protein pH-dependence, in relation to the local pH, that is manifested in the pKa distribution of histidine sub-proteomes. This is discussed in terms of protein stability, pH homeostasis, and fluctuations in proton concentration.
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