α‐Lactalbumin: structure and function

Permyakov, Eugene A.; Berliner, Lawrence J.

doi:10.1016/s0014-5793(00)01546-5

Cited by 465 publications

(364 citation statements)

References 53 publications

Supporting

Mentioning

352

Contrasting

Unclassified

Order By: Relevance

“…This conclusion has since then been supported by additional evidence obtained in bovine and other forms of BLA (27,(43)(44)(45)(46). Interestingly, a recent theoretical analysis of the observable properties of folding over marginal barriers indicates that the height of the barrier and the position of the unfolded minimum in the folding free-energy surface are directly connected (47).…”

Section: Implications Of a Marginal Folding Barrier In Blamentioning

confidence: 72%

Large-scale modulation of thermodynamic protein folding barriers linked to electrostatics

Halskau

Pérez-Jiménez

Ibarra‐Molero

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

natural selection ͉ homologous proteins ͉ structural pK shifts ͉ conformational ensembles ͉ differential scanning calorimetry C onventionally, the folding and function of single-domain proteins are described as two-state processes in analogy to elementary chemical reactions. The protein molecule is assumed to reside in either of two states: folded or active and unfolded or inactive, which interconvert by crossing a high free-energy barrier with transition-state-like kinetics. However, proteins can in principle exist in many different conformations or microstates because of their thousands of degrees of freedom. Such inherent complexity is best described by using low-dimensional freeenergy surfaces, which are obtained by projecting the solventaveraged energy as a function of atomic coordinates onto a few order parameters [the energy landscape approach (1)]. A freeenergy surface description includes the two-state folding model as a particular scenario, but is more general. In this approach barriers, basins of attraction, and even finer topographical details of the surface (i.e., roughness) emerge from detailed balancing between conformational entropy and the energy from stabilizing interactions (see refs. 2 and 3 for some specific examples). Therefore, surfaces that exhibit marginal barriers or are even completely barrierless appear as interesting alternatives to the two-state folding picture (1). These predictions have been confirmed experimentally in recent years (4-6).If the folding barriers are comparable to the thermal energy (RT), ensembles of conformations with an intermediate degree of structure become significantly populated and interconvert with diffusive dynamics. This realization opens a realm of possibilities for the experimental study of protein folding reactions and mechanisms (recently reviewed in ref. 7). Moreover, it also has important implications for protein function because the conformational fluctuations associated with marginal folding barriers could be exploited to modulate activity and/or synchronize the action of enzymes in sequential reactions (8). Examples of how this could be achieved have been recently explored for protein binding with the fly-cast model (9, 10) and related analyses (11), as well as for the optimization of allosteric coupling (12).Another important consequence of shallow free-energy surfaces is that their shape can be resolved in equilibrium experiments sensitive to the energy fluctuations associated with protein conformation, such as differential scanning calorimetry (DSC). Building on this idea, Muñoz and Sanchez-Ruiz have recently developed a phenomenological variable-barrier model for the analysis of DSC data (13). In this analysis, the DSC thermogram is fitted to an idealized (i.e., a Landau quartic polynomial) one-dimensional free-energy surface from which it is possible to estimate the barrier height and the population of conformational ensembles with an intermediate degree of structure (13). Although these folding barriers are intrinsically ''thermodynamic,'' ...

show abstract

Section: Implications Of a Marginal Folding Barrier In Blamentioning

confidence: 72%

Large-scale modulation of thermodynamic protein folding barriers linked to electrostatics

Halskau

Pérez-Jiménez

Ibarra‐Molero

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…An outstanding example to illustrate this hypothesis is the mechanism of oxidative folding of α-lactalbumin (αLA) elucidated in the absence or presence of calcium ( Figure 3) [35,36]. αLA (122 residues; four disulfide bonds) comprises an α-helical domain and a β-sheet domain that is considerably stabilized upon binding to calcium [37]. In the absence of calcium, the oxidative folding of αLA resembles that of hirudin, proceeding through the formation of heterogeneous populations of 1-, 2-and 3-disulfide intermediates and with the final accumulation of 4-disulfide scrambled isomers.…”

Section: Diversity In the Oxidative Folding Of α-Lactalbuminmentioning

confidence: 99%

Folding of small disulfide-rich proteins: clarifying the puzzle

Arolas

Aviles

Chang³

et al. 2006

Trends in Biochemical Sciences

164

158

View full text Add to dashboard Cite

The process by which small proteins fold to their native conformations has been intensively studied over the last few decades. In this field, the particular chemistry of disulfide bond formation has facilitated the characterization of the oxidative folding of numerous small, disulfide-rich proteins with results that illustrate a high diversity of folding mechanisms, differing in the heterogeneity and disulfide pairing nativeness of their intermediates. In this review, we combine information on the folding of different protein models together with the recent structural determinations of major intermediates to provide new molecular clues in oxidative folding. Also, we turn to analyze the role of disulfide bonds in misfolding and protein aggregation and their implications in amyloidosis and conformational diseases.2

show abstract

“…Variant B is a reference protein whose polypeptide chain contains 123 amino acid residues. The globular structure of α-lactalbumin is stabilised by disulfi de bonds at the pH of 5.4 to 9.0 [Permyakov and Berliner 2000].…”

Section: Nomenclature and Molecular Properties Of Milk Proteinsmentioning

confidence: 99%

Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects

Dziuba

2014

Acta Sci Pol Technol Aliment

View full text Add to dashboard Cite

Proteins are one of the primary components of the food, both in terms of nutrition and function. They are main source of amino acids, essential for synthesis of proteins, and also source of energy. Additionally, many proteins exhibit specifi c biological activities, which may have effect on functional or pro-health properties of food products. These proteins and their hydrolysis products, peptides, may infl uence the properties of food and human organism. The number of commercially available food products containing bioactive peptides is very low, apart from that milk proteins are their rich source. It could be supposed that number of available products with declared activity will rise in near future because of observed strong uptrend on interest in such products. Molecular and biological properties of milk proteins, as precursors of bioactive peptides was characterised in the work. Therefore, the strategy of research and obtaining of such peptides both in laboratory and industrial scale, as well as the range of their commercial application, was presented. Several examples of research efforts presenting high potential to develop new products containing bioactive peptides from milk proteins and predetermined as nutraceuticals was described.

show abstract

α‐Lactalbumin: structure and function

Cited by 465 publications

References 53 publications

Large-scale modulation of thermodynamic protein folding barriers linked to electrostatics

Large-scale modulation of thermodynamic protein folding barriers linked to electrostatics

Folding of small disulfide-rich proteins: clarifying the puzzle

Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects

Contact Info

Product

Resources

About