Disorder in Milk Proteins: α-Lactalbumin. Part C. Peculiarities of Metal Binding

Author(s): Eugene A. Permyakov, Serge E. Permyakov, Leonid Breydo, Elrashdy M. Redwan, Hussein A. Almehdar, Vladimir N. Uversky

Journal Name: Current Protein & Peptide Science

Volume 17 , Issue 8 , 2016

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Graphical Abstract:


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.

Keywords: α-lactalbumin, molten globule, calcium binding, EF-hand, intrinsically disordered protein, intrinsically disordered region, conformational stability.

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Article Details

Year: 2016
Published on: 03 October, 2016
Page: [735 - 745]
Pages: 11
DOI: 10.2174/1389203717666160530151534
Price: $65

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