ArticleJournal of molecular biology2009
Existence of a noncanonical state of iron-bound transferrin at endosomal pH revealed by hydrogen exchange and mass spectrometry.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- A closely related pair of superoxide dismutase isozymes from Staphylococcus aureus show distinct stabilities and proton-exchange dynamics.The Journal of biological chemistry · 2026Article
- Mass spectrometry-based methods in characterization of the higher order structure of protein therapeutics.Journal of pharmaceutical and biomedical analysis · 2020Review
- Dimerization interface of osteoprotegerin revealed by hydrogen-deuterium exchange mass spectrometry.The Journal of biological chemistry · 2018Article
- Evaluation of Nonferrous Metals as Potential In Vivo Tracers of Transferrin-Based Therapeutics.Journal of the American Society for Mass Spectrometry · 2016Article
- Detailed molecular dynamics simulations of human transferrin provide insights into iron release dynamics at serum and endosomal pH.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015Article
- Electrostatic effects control the stability and iron release kinetics of ovotransferrin.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014Article
- A new approach to measuring protein backbone protection with high spatial resolution using H/D exchange and electron capture dissociation.Analytical chemistry · 2013Article
- Mass spectrometry study of a transferrin-based protein drug reveals the key role of protein aggregation for successful oral delivery.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Transferrin as a model system for method development to study structure, dynamics and interactions of metalloproteins using mass spectrometry.Biochimica et biophysica acta · 2012Review
- Conserved interaction between transferrin and transferrin-binding proteins from porcine pathogens.The Journal of biological chemistry · 2011Article
- Impact of oxidation on protein therapeutics: conformational dynamics of intact and oxidized acid-β-glucocerebrosidase at near-physiological pH.Protein science : a publication of the Protein Society · 2010Article
- Noncanonical interactions between serum transferrin and transferrin receptor evaluated with electrospray ionization mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Conformation and dynamics of biopharmaceuticals: transition of mass spectrometry-based tools from academe to industry.Journal of the American Society for Mass Spectrometry · 2010Article
- Advances and challenges in analytical characterization of biotechnology products: mass spectrometry-based approaches to study properties and behavior of protein therapeutics.Biotechnology advancesReview
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Transferrin (Tf) is an enigmatic metalloprotein that exhibits a profound conformational change upon binding of ferric ion and a synergistic anion (oxalate or carbonate). While the apo and holo forms of the protein have well-defined and stable conformations termed "open" and "closed," certain aspects of Tf behavior imply the existence of alternative protein states. In this work, hydrogen/deuterium exchange was used in combination with mass spectrometry to map solvent-accessible surfaces of the iron-bound and iron-free forms of the N-terminal lobe of human serum Tf at both neutral and endosomal pH levels. While the deuterium uptake is significantly decelerated in the iron-bound state of the protein (compared with the apo form) at neutral pH, the changes are distributed very unevenly across the protein sequence. Protein segments exhibiting most noticeable gain in protection map onto the interdomain cleft region housing the iron-binding site. At the same time, protection levels of segments located in the bulk of the protein are largely unaffected by the presence of the metal. These observations are fully consistent with the notion of a metal-induced switch from the open to the closed conformation with solvent-inaccessible interdomain cleft. However, differences in the exchange behavior between the apo and holo forms of Tf become much less noticeable at endosomal pH, including the segments located in the interdomain cleft region. Intriguingly, a significant patch in the cleft region becomes slightly less protected in the presence of the metal, suggesting that the holoprotein exists in the open conformation under these slightly acidic conditions. The existence of a noncanonical state of holoTf was postulated several years ago; however, this work provides, for the first time, conclusive evidence that such alternative states are indeed populated in solution.
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Registered trials
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