Disorder in Milk Proteins: α-lactalbumin. Part C. Peculiarities of Metal Binding
Ef-hand, Calcium Binding, Conformational Stability, Intrinsically Disordered Region, Intrinsically Disordered Protein, Molten Globule, α-lactalbumin
This is a concluding part of the three-part article from a series of reviews on the abundance and roles of intrinsic disorder in milk proteins. In this paper, we describe the peculiarities of metal binding to a multifunctional milk protein, α-lactalbumin, which has two domains, a large α-helical domain and a small β-sheet domain connected by a calcium binding loop. It is known that in addition to four disulfide bonds, the native fold of this protein is stabilized by binding of a calcium ion. In fact, although in various mammals, α-lactalbumins are rather poorly conserved possessing the overall sequence identity of ~16%, the positions of all eight cysteines and a calcium binding site (residues DKFLDDDITDDI in human protein) are strongly conserved. Curiously, this conserved calcium binding loop is located within a region with increased structural flexibility. Besides canonical calcium binding, α-lactalbumin is known to interact with other metals, such as zinc (for which it has a specific binding site), and, in its apo-form, it can bind other divalent and monovalent cations. The binding of Mg2+, Na+, and K+ to the Ca2+ site increases α-lactalbumin stability against action of heat and various denaturing agents, with the higher stabilization effects being imposed by the stronger bound metal ions.
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Citation / Publisher Attribution
Current Protein and Peptide Science, v. 17, issue 8, p. 735-745
Scholar Commons Citation
Permyakov, Eugene A.; Permyakov, Sergei E.; Breydo, Leonid; Redwan, Elrashdy M.; Almehdar, Hussein A.; and Uversky, Vladimir N., "Disorder in Milk Proteins: α-lactalbumin. Part C. Peculiarities of Metal Binding" (2017). Molecular Medicine Faculty Publications. 867.