Note: Conversion of alpha-lactalbumin to a protein inducing apoptosis

Conversion to HAMLET (human a-lactalbumin made lethal to tumor cells) required partial unfolding of the protein and a specific fatty acid, C18:1, as a necessary cofactor.
Identified the folding change and the fatty acid as two key elements that define HAMLET
It may be speculated that molecules like HAMLET can aid in lowering the incidence of cancer in breast-fed children by purging of tumor cells from the gut of the neonate.
The state of protein folding can determine the cellular function.
The factor determines the folding;

Higher-energy barriers between different conformations -- overcoming by chaperones
Also have other systems which relieve the thermodynamics barrier

Partially unfolded is stabilized by cofactor which is the fatty acid - to be specific oleic acid
This paper can identify the cofactor (lipid - C18) contributing to protein folding -- affecting the biological function
Ca2+ ion also affecting the protein folding (stability of protein to maintain particular structure)
The low pH is known to favor the release of Ca2+, and casein is precipitated -- we happened to purify the apoptosis inducing form of a-lactalbumin from human milk after precipitation of casein at low pH, thus mimicking the conditions in the stomach of the breast-fed child
alpha-lactalbumin changes its fold to a molten globule-like state but stays in this intermediate form rather than altering its secondary structure to a b-sheet-rich state
HAMLET is one of several naturally occurring surveillance molecules that purge unwanted cells from the local tissues, thereby driving the intestinal mucosa toward maturity.
Proteins may respond to different environments by changing their fold and that this process allows a single polypeptide chain to exert vastly different and beneficial biologic functions in different tissue compartments.

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