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.
Current Protein & Peptide Science
Title:Disorder in Milk Proteins: α-Lactalbumin. Part C. Peculiarities of Metal Binding
Volume: 17 Issue: 8
Author(s): Eugene A. Permyakov, Serge E. Permyakov, Leonid Breydo, Elrashdy M. Redwan, Hussein A. Almehdar and Vladimir N. Uversky
Affiliation:
Keywords: α-lactalbumin, molten globule, calcium binding, EF-hand, intrinsically disordered protein, intrinsically disordered region, conformational stability.
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.
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Cite this article as:
Permyakov A. Eugene, Permyakov E. Serge, Breydo Leonid, Redwan M. Elrashdy, Almehdar A. Hussein and Uversky N. Vladimir, Disorder in Milk Proteins: α-Lactalbumin. Part C. Peculiarities of Metal Binding, Current Protein & Peptide Science 2016; 17 (8) . https://dx.doi.org/10.2174/1389203717666160530151534
DOI https://dx.doi.org/10.2174/1389203717666160530151534 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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