Protein Three-Dimensional Structure

Introduction

The three-dimensional structure of proteins is essential for their biological function. Proteins can be classified based on their structure and function into fibrous and globular proteins. This section explores the structural features, stabilization mechanisms, and biological roles of these protein types, with a focus on keratin, collagen, and myoglobin.

Fibrous Proteins

General Features

• Fibrous proteins provide mechanical support and structural integrity to cells and tissues.

• They are typically assembled into large cables or threads.

• These proteins have repetitive, hydrophobic sequences that promote the formation of elongated structures.

• Common examples include keratins (hair, nails), collagen (tendons, skin, bones), and myosin (muscle fibers).

Structural Motifs

• Many fibrous proteins form coiled coils, where two or more helices wrap around each other.

• These superstructures are also called superhelices or supercoils.

Keratin

• α-Keratin consists of two right-handed α-helices twisted into a left-handed supercoil.

• Stabilized by van der Waals forces, ionic interactions, and disulfide bridges ( bonds).

• Provides strength and resilience to hair, nails, and the outer layer of skin.

Collagen

• Collagen is the main protein in connective tissues such as tendons, skin, and bones.

• Composed of three left-handed helices (not α-helices) coiled together into a right-handed supercoil.

• Each chain is about 1000 amino acids long, with a repeating Gly-X-Y sequence (where X and Y are often proline and hydroxyproline).

• Every third residue is glycine, allowing tight packing of the three chains.

• Common sequence motifs include Gly-Pro-Hyp (Hyp = hydroxyproline).

Collagen Amino Acid Sequences (Examples)

• Gly-Pro-Met-Gly-Pro-Ser-Gly-Pro-Ala

• Leu-Hyp-Gly-Pro-Hyp-Gly-Ala-His

• Pro-Gln-Gly-Phe-Gln-Gly-Pro-His

• Glu-Hyp-Gly-Glu-Hyp-Gly-Ala-Ser

• Pro-Met-Gly-Pro-Arg-Gly-Pro-His

• Pro-Hyp-Gly-Lys-Asn-Gly-Asp-Ala

Collagen Structure and Stabilization

• Stabilized by interchain hydrogen bonding (no intrachain H-bonding).

• Hydrogen bonds form between the NH group of glycine in one chain and the C=O group in another chain.

• Steric repulsion of proline side chains maintains the extended structure.

• Hydroxylation of lysine and proline residues (requires vitamin C) aids in the formation and stabilization of the triple helix.

• Triple helices can form covalent crosslinks, aggregating into insoluble fibers.

Clinical Insight: Scurvy (Vitamin C Deficiency)

• Vitamin C (ascorbate) is required for the hydroxylation of proline and lysine in collagen.

• Deficiency leads to scurvy, characterized by weak connective tissue due to unstable collagen fibers.

• Humans cannot synthesize vitamin C and must obtain it from the diet.

Globular Proteins

General Features

• Globular proteins are soluble, compact, and roughly spherical in shape.

• They have a hydrophobic interior and a hydrophilic surface.

• Function as enzymes, carrier proteins, and regulatory proteins.

Myoglobin

• Myoglobin (Mb) facilitates oxygen diffusion in the muscles of vertebrates.

• Composed of a single polypeptide chain (~153 amino acids) and a prosthetic group (heme).

• The heme group is an organic, non-polypeptide molecule essential for oxygen binding.

• Structure consists of 8 α-helices, with the heme group bound in a hydrophobic cleft.

• Interior is mostly hydrophobic amino acids; the exterior has more diverse hydropathy.

• Oxygen binds to the iron atom (Fe) in the heme group, stabilized by hydrogen bonding.

Protein Structural Motifs and Domains

Supersecondary Structure (Motifs)

Supersecondary structures, or motifs, are common combinations of secondary structure elements found in proteins. They contribute to the overall folding and function of proteins.

• Coiled coil

• Helix bundle

• β-α-β motif

• β-hairpin

• β-meander

• Helix-turn-helix

• Greek key

• β-barrel

• α/β barrel

Protein Domains

• Domains are independently folded, compact units within a protein, typically 30–400 amino acids in length.

• Domains are connected by flexible segments and may have unique activities (e.g., binding small molecules, catalyzing reactions).

• Some proteins, such as immunoglobulins, contain repeated domains (e.g., Ig domains with constant and variable regions).

Summary Table: Comparison of Fibrous and Globular Proteins

Additional info: The notes also reference the importance of vitamin C in collagen biosynthesis and the clinical consequences of its deficiency (scurvy). The concept of protein motifs and domains is foundational for understanding protein folding and function in biochemistry.