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The Amino Acid Sequences of Proteins Determine Folding and Non-folding

  • Richard Dods
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Abstract

This chapter (The Amino Acid Sequences of Proteins Determine Folding and Non-folding) continues where Chap.  1 left off. Amino acid sequences determine the folded structure of proteins. The manner in which the protein folds is visualized by an energy landscape called a protein folding funnel. This chapter describes the funnel and how it relates to three-dimensional protein structure. This chapter describes the spin glass theory which also visualizes protein folding. Regions of amino acids called foldons are described. The 20 amino acid building blocks of proteins are enumerated in this chapter. The ice-like blanket that surrounds a protein and its effects on folding are described in this chapter. Other forces that stabilize the folded structure are described. This chapter defines and describes intrinsically disordered proteins (IDP) and intrinsically disordered protein regions (IDPR) and their functions. Effects of hypoxia on protein structure are discussed. Scaffolding and hubs are described.

Notes

Glossary

Angiogenesis

refers to proliferation of blood vessels.

Energy landscape

corresponds to all possible conformations of a protein i.e. all spatial positions of the protein molecule and therefore all its Gibbs free energies.

Entropism

refers to protein function due to a random coil.

Foldons

are protein regions that are folded.

Hub proteins

are proteins (at least ten) that bind each other.

Hydrophobic (hydropathy)

refers to avoidance of water.

Hydrophobic collapse

is a process in which newly synthesized proteins form secondary structure (α-helix and β-pleated) in regions of hydrophobicity. These protein regions then “collapse” (aggregate) by arranging the hydrophobic amino acids, so that their side chains face toward the interior of the molecule, thus creating tertiary conformation.

Hypoxia

refers to lack of oxygen.

Intrinsically disordered proteins or regions

are proteins or regions of proteins that have a random coil conformation and do not have a three-dimensional folded structure.

Molten globules

are partially folded proteins that have a compact protein interior and have some secondary structure but lack tertiary structure. They can be isolated under moderately denaturing conditions and are separate from the native state by having a higher free energy.

Moonlighting

refers to overlapping protein domains where other proteins bind.

Native state

of a protein is when the protein is in its lowest energy state and exhibits its natural functions.

Posttranslational modification

refers to chemical changes that occur to amino acids after they have come off the ribosomes as a polypeptide.

Pre-molten globule (early molten globule)

is an intermediate between the molten protein and the native protein. The protein is partially folded. Compactness is developing in the interior of the molecule. It may have some secondary structure, and has incomplete tertiary structure. It may be isolated.

Principle of minimal frustration

states that proteins have domains that avoid valleys that tend to fold to a lower Gibbs energy conformation.

Protein folding funnels

is the current hypothesis as to how a protein folds. Its width is the entropy (highest at the top, lowest at the bottom). The top of the funnel has the highest Gibbs free energy and the bottom the lowest Gibbs free energy. It has an infinite number of conformations at the top and the native conformation resides at the bottom. The sides of the funnel have “valleys” that trap certain conformations. The “smoother” the sides of the funnel the faster the native conformation is reached.

Random coil (loops)

is a protein conformation in which the amino acid sequence does not have a specific, rigid, geometric shape. Rather the amino acid sequence of a random coil is randomly orientated in all possible conformations. Random coils are detected by circular dichroism and nuclear magnetic resonance but not by X-ray diffraction. X-ray diffraction yields results only for rigid (ordered) portions of proteins.

Scaffold proteins

bind two or more other proteins.

Secondary structure

refers to two structures in a protein, α-helix and β-pleated sheets (further described in Chap.  2).

Site-directed mutagenesis

is replacing one amino acid by another using genetic engineering.

Steric hindrance

refers to repulsions by side chains of amino acids. There is much less steric hindrance in intrinsic disordered region than in ordered regions.

Tertiary structure

refers to the overall shape of a protein. The α-helixes, β-pleated sheets, and random coils in the protein fold themselves to form the overall shape, tertiary structure of the protein (further described in Chap.  3).

Theory of spin glasses

is applicable to folding of proteins. Spin glasses are a class of magnetic alloys that below a critical temperature have energy valleys separated by energy barriers and other characteristics similar to those found in the protein folding funnel hypothesis.

Ubiquitination

refers to binding of ubiquitin to a protein for its destruction.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Richard Dods
    • 1
  1. 1.Illinois Mathematics and Science AcademyPalatineUSA

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