Transferrin as a model system for method development to study structure, dynamics and interactions of metalloproteins using mass spectrometry

• Published in: Biochimica et biophysica acta Vol. 1820; no. 3; pp. 417 - 426
• Main Authors: Kaltashov, Igor A., Bobst, Cedric E., Zhang, Mingxuan, Leverence, Rachael, Gumerov, Dmitry R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2012
• Subjects: Binding Sites; electrospray ionization mass spectrometry; homeostasis; Humans; Hydrogen exchange; Iron - metabolism; Metalloprotein; metalloproteins; Metalloproteins - chemistry; Metalloproteins - metabolism; Models, Biological; Native mass spectrometry; Protein Binding; Protein Structure, Tertiary; Protein therapeutics; Siderophore; Spectrometry, Mass, Electrospray Ionization; Transferrin; Transferrin - chemistry; Transferrin - metabolism; TfR; Transferrin; BBB; FAB; MS; Metalloprotein; Hydrogen exchange; Protein therapeutics; GHT; Tf; Siderophore; hTf/2N; Native mass spectrometry; ESI; hTf; Fe2hTf; HDX
• ISSN: 0304-4165; 0006-3002; 1872-8006; 0006-3002
• DOI: 10.1016/j.bbagen.2011.06.019

Transferrin (Tf) is a paradigmatic metalloprotein, which has been extensively studied in the past and still is a focal point of numerous investigation efforts owing to its unique role in iron homeostasis and enormous promise as a component of a wide range of therapies. Electrospray ionization mass spectrometry (ESI MS) is a potent analytical tool that has been used successfully to study various properties of Tf and Tf-based products, ranging from covalent structure and metal binding to conformation and interaction with their physiological partners. Various ESI MS-based techniques produce unique information on Tf properties and behavior that is highly complementary to information provided by other experimental techniques. The experimental ESI MS-based techniques developed for Tf studies are not only useful for understanding of fundamental aspects of the iron-binding properties of this protein and optimizing Tf-based therapeutic products, but can also be applied to study a range of other metalloproteins. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders. [Display omitted] ► Progress in biological mass spectrometry related to transferrin research. ► Unique information highly complementary to other experimental techniques. ► Can also be applied to study a range of other metalloproteins.