Protein Folding Notes
These notes are an edited and reformatted copy of notes that were originally posted on October 25, 2006 to a Yahoo Group I once owned. I was trying to understand why a combination of sea salt, glyconutrients, and coconut oil seemed to have a dramatic impact on my condition. I believe I read through all or large parts of everything linked below and these notes are an attempt to summarize the parts I found pertinent to my condition and what I was trying to understand about it.
GLYCOPROTEINS
The sugar group(s) can assist in protein folding or improve proteins' stability.
One example of glycoproteins found in the body are mucins which are secreted in the mucus of the respiratory and digestive tracts. The sugars attached to mucins give them considerable water-holding capacity and also make them resistant to proteolysis by digestive enzymes.
Glycoproteins are important for immune cell recognition, especially in mammals. Examples of glycoproteins in the immune system are:
- molecules such as antibodies (immunoglobulins), which interact directly with antigens
- molecules of the major histocompatibility complex (or MHC), which are expressed on the surface of cells and interact with T-cells as part of the adaptive immune response.
Other examples of glycoproteins include:
- components of the Zona pellucida which surrounds the Oocyte, and is important for Sperm-egg interaction and.
- structural glycoproteins, which occur in Connective tissue. These help bind together the fibers, cells, and ground substance of Connective tissue.
They may also help components of the tissue bind to inorganic substances, such as Calcium in Bone.
CONNECTIVE TISSUE
- Areolar (or loose) connective tissue holds organs and epithelia in place, and has a variety of Protein fibers, including collagen and Elastin. It is also important in inflammation.
PROTEIN FOLDING
The "reverse" of the folding process is called protein denaturation, whereby the native structure of a protein is disrupted and a random coil ensemble of unfolded structures is formed instead. Denaturation can be carried out chemically by the addition of denaturants or thermally by heating (and sometimes cooling). Many denatured proteins precipitate into insoluble amorphous aggregates. Some proteins denatured under some conditions can reversibly refold; however, in many cases denaturation is irreversible.
The relationship between folding and amino acid sequence
The particular amino-acid sequence (or "primary structure") of a protein predisposes it to fold into its native conformation or conformations. Many proteins do so spontaneously during or after their synthesis inside cells. While these macromolecules may be seen as "folding themselves," in fact their folding depends a great deal on the characteristics of their surrounding solution, including the identity of the primary solvent (either water or lipid inside cells), the concentration of salts, the temperature, and molecular chaperone.
Preconditions for correct folding
In certain solutions and under some conditions proteins will not fold at all. Temperatures above or below the range that cells tend to live in will cause proteins to unfold or "denature" (this is why boiling makes the white of an egg opaque). High concentrations of solutes and extremes of pH can do the same. A fully denatured protein lacks both tertiary and secondary structure, and exists as a so-called random coil.
Cells sometimes protect their proteins against the denaturing influence of heat with enzymes known as chaperones or heat shock protein, which assist other proteins both in folding and in remaining folded. Some proteins never fold in cells at all except with the assistance of chaperone molecules, that either isolate individual proteins so that their folding is not interrupted by interactions with other proteins or help to unfold misfolded proteins, giving them a second chance to refold properly.
SOLUTE
In chemistry, a solution is a homogeneous mixture composed of one or more substances, known as solutes, dissolved in another substance, known as a solvent. A common example is a solid, such as salt or sugar, dissolved in water, a liquid.
DENATURED PROTEINS
A denatured protein is one which has lost its functional conformation.
Once denatured, a protein loses most, if not all of its biological activity. A protein can be denatured through various means including exposure to extremes of heat, pH, salt concentration, denaturing agents like urea/guanidinechloride and use of detergents.
When a protein is denatured, the secondary and tertiary structures are altered but the peptide bonds between the amino acids are left intact. Since the structure of the protein determines its function, the protein can no longer perform its function once it has been denatured.
RANDOM TIDBITS
http://chemicalelements.com/elements/na.html
http://daily.stanford.edu/article/2006/10/16/fightingDiseaseOneProcessorAtATime
Foldina@home
http://www.wisc-online.com/objects/index_tj.asp?objid=AP1302*
"The cell gets a message to make a certain quantity of a specific protein."
"A portion of the DNA molecule unwinds, exposing the gene responsible for
that protein."
Some of my eventual conclusions or takeaways rooted in the above plus first-hand experience:
GLYCOPROTEINS
The sugar group(s) can assist in protein folding or improve proteins' stability.
One example of glycoproteins found in the body are mucins which are secreted in the mucus of the respiratory and digestive tracts. The sugars attached to mucins give them considerable water-holding capacity and also make them resistant to proteolysis by digestive enzymes.
Glycoproteins are important for immune cell recognition, especially in mammals. Examples of glycoproteins in the immune system are:
- molecules such as antibodies (immunoglobulins), which interact directly with antigens
- molecules of the major histocompatibility complex (or MHC), which are expressed on the surface of cells and interact with T-cells as part of the adaptive immune response.
Other examples of glycoproteins include:
- components of the Zona pellucida which surrounds the Oocyte, and is important for Sperm-egg interaction and.
- structural glycoproteins, which occur in Connective tissue. These help bind together the fibers, cells, and ground substance of Connective tissue.
They may also help components of the tissue bind to inorganic substances, such as Calcium in Bone.
CONNECTIVE TISSUE
- Areolar (or loose) connective tissue holds organs and epithelia in place, and has a variety of Protein fibers, including collagen and Elastin. It is also important in inflammation.
PROTEIN FOLDING
The "reverse" of the folding process is called protein denaturation, whereby the native structure of a protein is disrupted and a random coil ensemble of unfolded structures is formed instead. Denaturation can be carried out chemically by the addition of denaturants or thermally by heating (and sometimes cooling). Many denatured proteins precipitate into insoluble amorphous aggregates. Some proteins denatured under some conditions can reversibly refold; however, in many cases denaturation is irreversible.
The relationship between folding and amino acid sequence
The particular amino-acid sequence (or "primary structure") of a protein predisposes it to fold into its native conformation or conformations. Many proteins do so spontaneously during or after their synthesis inside cells. While these macromolecules may be seen as "folding themselves," in fact their folding depends a great deal on the characteristics of their surrounding solution, including the identity of the primary solvent (either water or lipid inside cells), the concentration of salts, the temperature, and molecular chaperone.
Preconditions for correct folding
In certain solutions and under some conditions proteins will not fold at all. Temperatures above or below the range that cells tend to live in will cause proteins to unfold or "denature" (this is why boiling makes the white of an egg opaque). High concentrations of solutes and extremes of pH can do the same. A fully denatured protein lacks both tertiary and secondary structure, and exists as a so-called random coil.
Cells sometimes protect their proteins against the denaturing influence of heat with enzymes known as chaperones or heat shock protein, which assist other proteins both in folding and in remaining folded. Some proteins never fold in cells at all except with the assistance of chaperone molecules, that either isolate individual proteins so that their folding is not interrupted by interactions with other proteins or help to unfold misfolded proteins, giving them a second chance to refold properly.
SOLUTE
In chemistry, a solution is a homogeneous mixture composed of one or more substances, known as solutes, dissolved in another substance, known as a solvent. A common example is a solid, such as salt or sugar, dissolved in water, a liquid.
DENATURED PROTEINS
A denatured protein is one which has lost its functional conformation.
Once denatured, a protein loses most, if not all of its biological activity. A protein can be denatured through various means including exposure to extremes of heat, pH, salt concentration, denaturing agents like urea/guanidinechloride and use of detergents.
When a protein is denatured, the secondary and tertiary structures are altered but the peptide bonds between the amino acids are left intact. Since the structure of the protein determines its function, the protein can no longer perform its function once it has been denatured.
RANDOM TIDBITS
http://chemicalelements.com/elements/na.html
http://daily.stanford.edu/article/2006/10/16/fightingDiseaseOneProcessorAtATime
Foldina@home
http://www.wisc-online.com/objects/index_tj.asp?objid=AP1302*
"The cell gets a message to make a certain quantity of a specific protein."
"A portion of the DNA molecule unwinds, exposing the gene responsible for
that protein."
Some of my eventual conclusions or takeaways rooted in the above plus first-hand experience:
- Immune cells tend to be glycoproteins. So glyconutrients are critical to the body's ability to create the army it needs to defend itself from invaders. This means the right carbs are essential to immune function.
- The CFTR is a defective protein that is the root cause of all CF symptoms and whatever genetic coding defect it has is made worse by protein misfolds rooted in chemical derangement within the cell.
- Proteins misfold when cell chemistry is deranged, either from salt derangement or pH derangement. CF involves both of those issues.
- "The Normal Progression of CF" is most likely due to a positive feedback loop -- aka vicious cycle -- in which worsening chemical derangement leads to more misfolded proteins which leads to worsening chemical derangement and round and round we go.
- Ergo, you can stop "The Normal Progression of CF" if you can address the chemical derangement in the body that causes misfolded proteins which I think is the root cause of how CF gets steadily worse over your lifetime and why I was able to not just stabilize my condition but actually reverse my symptoms, which I absolutely did not expect when I set out on this journey. I figured I would take hundreds of dollars worth of dietary supplements a month for the rest of my life instead of hundreds to thousands of dollars worth of drugs.
