Amino Acids & Protein Structures

Amino Acid & Protein 2

• Proteins have complex structures, with several levels of organization, impacting their function.
• Forces influencing protein structure include hydrogen bonds between peptide groups, hydrogen bonds between side chains, hydrophobic interactions, and disulfide bonds.
• The forces determining protein shapes are vital for its functions.

Secondary Structures

• Alpha-Helix: Hydrogen bonds connect amino acids in a coiled, right-handed helix; on average ~11 amino acids per turn; can be up to 53 amino acids.
• Beta-Sheet: Hydrogen bonds form between parallel or anti-parallel polypeptide chains; forming a pleated sheet structure. Generally, 2-15 amino acids per turn (average = ~6); anti-parallel is more common.

Tertiary Structures

• Proteins' 3-dimensional structure is determined by the arrangement of secondary structures, forming super-secondary structures or motifs.
• On average 27% are alpha helix and 23% are beta structures.
• Exceptions do exist; for example, Myoglobin and Hemoglobin are 75-80% alpha helix, whereas Concanavalin A is entirely beta.
• Typically, hydrophobic amino acids are found in interior regions of protein structures. Polar and charged amino acids are on the surface, allowing them to interact with water.

Quaternary Structures

• The fourth level of protein structure involves the interaction of multiple polypeptide chains to form a larger protein.
• Individual chains are called subunits (monomers).
• Subunits can be identical (homogeneous) or different (heterogeneous).
• Common arrangements include dimers, trimers, and tetramers.

Central Dogma of Protein Folding

• Protein folding is spontaneous, often starting with secondary structures.
• The primary sequence dictates the final tertiary structure.
• Proteins have molecular chaperones that assist folding, especially under stress.

The Structure of Selected Proteins

• Fibrous Proteins:
  • Structural proteins, with high tensile strength; insoluble in water.
  • Examples: Keratin (hair, nails), Collagen (connective tissue), Silk (spiders' webs).
• Globular Proteins:
  • Typically spherical, with hydrophobic amino acids inward, and hydrophilic amino acids outward; making them soluble in water.
  • Examples: Myoglobin (oxygen transport), Hemoglobin (oxygen transport), Enzymes, Hormones.

Keratin

• Major structural protein of hair, nails, and horns;
• Its basic structure is an alpha-helix. Two alpha-helices twist to form a coiled-coil. Protofilaments group to form microfibrils and then to macofibrils.

Collagen

• Most abundant protein in vertebrates, mostly found in connective tissue (ligaments, tendons, cartilage);
• Triple helix of three collagen polypeptides. Has a repeating glycine-proline-alanine sequence & left-handed helix.

Myoglobin

• Oxygen-carrying protein;
• Small size and easily crystallizes, making it suitable for x-ray crystallography studies.
• 75% of its amino acid sequence is in alpha helix arrangement, with compact structure, 8 segments.
• Contains prosthetic heme group for oxygen binding.
• Has about 153 amino acids

Hemoglobin

• Oxygen-carrying protein in red blood cells, transporting oxygen and carbon dioxide;
• Has 2 alpha and 2 beta chains (tetramer), each with a heme group.
• Has about 574 amino acids
• Nearly spherical, with hydrophobic core and hydrophilic surface.
• 7-8 helical segment, with a plane Fe2+ in the middle or a slightly moved out heme for T state.

Denaturing Proteins

• Bonds maintaining a protein's shape are broken by changes in temperature, pH, or salt concentration.
• Proteins become denatured, changing shape & losing function;
• Fibrous proteins lose structural strength; globular proteins become insoluble and inactive.