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

[ Vol. 17 , Issue. 8 ]

Author(s):

Eugene A. Permyakov, Serge E. Permyakov, Leonid Breydo, Elrashdy M. Redwan, Hussein A. Almehdar and Vladimir N. Uversky   Pages 735 - 745 ( 11 )

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.

Affiliation:

Institute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino, Moscow region 142290, Russia., Department of Molecular Medicine, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC3540, Tampa, FL 33612, USA.

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