title: Disorder in Milk Proteins: α-Lactalbumin. Part C. Peculiarities of Metal Binding.
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.
authors.affiliation: Institute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino, Moscow region 142290, Russia. epermyak@yandex.ru.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Permyakov
authors.forename: Serge E
authors.initials: SE
authors.lastname: Permyakov
authors.forename: Leonid
authors.initials: L
authors.lastname: Breydo
authors.forename: Elrashdy M
authors.initials: EM
authors.lastname: Redwan
authors.forename: Hussein A
authors.initials: HA
authors.lastname: Almehdar
authors.affiliation: Department of Molecular Medicine, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC3540, Tampa, FL 33612, USA. vuversky@health.usf.edu.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007768:Lactalbumin / Q000737:chemistry* / Q000378:metabolism; D008670:Metals / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D008670:Metals; D007768:Lactalbumin; D002118:Calcium