Chapter 6.2

Fibrous Proteins as Structural Materials

Overview of Fibrous Proteins

Fibrous proteins are a class of proteins characterized by their elongated, filamentous shapes and well-defined secondary structures. They play essential structural roles in animal cells and tissues, providing mechanical strength and support.

• Definition: Fibrous proteins are elongated molecules with repetitive secondary structures, often forming fibers or sheets.

• Examples:

  • α-Keratin – Found in hair, fingernails, feathers, scales, and intermediate filaments (intracellular).

  • Fibroin – The main protein in silk cocoons.

  • Collagen – The most abundant connective tissue protein; forms the matrix material in bone.

• Structural Role: These proteins are the major components of skin, connective tissue, and animal fibers like hair and silk.

• Mechanical Properties: The amino acid sequence and secondary structure confer specific mechanical properties to each protein.

Amino Acid Composition of Fibrous Proteins

The unique properties of fibrous proteins are largely determined by their amino acid composition. Certain amino acids are present in high abundance, influencing the protein's structure and function.

Amino Acid	α-Keratin (wool)	Fibroin (silk)	Collagen (bovine tendon)	All proteins
Gly	8.1	44.6	32.7	7.9
Ala	5.0	29.4	12.0	8.7
Ser	10.2	12.2	3.4	5.8
Glu + Gln	12.1	1.0	7.7	6.6 (3.7)
Cys	11.2	0	0	1.3
Pro	7.5	0.3	12.1a	4.7
Arg	7.2	5.0	5.0	5.0
Leu	6.9	0.5	2.1	8.9
Thr	6.5	0.9	1.6	5.6

Amino Acid	α-Keratin (wool)	Fibroin (silk)	Collagen (bovine tendon)	All proteins
Asp + Asn	6.0	1.3	4.5	5.9 (4.2)
Val	5.1	2.2	1.8	7.2
Tyr	4.2	5.2	0.4	3.5
Ile	2.8	0.9	0.9	5.5
Phe	2.5	0.5	1.2	4.0
Lys	2.3	0.3	3.7b	5.5
Trp	1.2	0	0	1.5
His	0.7	0.2	0.3	2.4
Met	0.5	0	0.7	2.0

Additional info: In collagen, 39% of the content is hydroxyproline and 14% is hydroxylysine, which are post-translationally modified amino acids important for stability.

α-Keratin: Structure and Function

Properties and Organization

α-Keratins are the major proteins of hair, fingernails, and skin, and belong to the intermediate filament protein family. Their structure is predominantly α-helical, organized into coiled-coil motifs.

• Intermediate Filament Proteins: α-Keratins are part of a broad group that provides structural support in nuclei, cytoplasm, and cell surfaces.

• Coiled-Coil Structure: Two α-helical monomers pair in parallel to form a coiled-coil dimer, which further assembles into protofilaments and protofibrils.

• Hydrophobic Interactions: Large hydrophobic residues repeat every four positions, creating a hydrophobic interface between helices.

Example: The regular spacing of 25 nm along keratin fibers is due to the arrangement of coiled-coil structures.

Fibroin: Structure and Function

Properties and Organization

Fibroin is the main protein in silk, characterized by extensive β-sheet structure. Nearly half of its residues are glycine, and the sequence is highly repetitive.

• β-Sheet Structure: Silkworm fibroin contains long regions of antiparallel β-sheets, with chains running parallel to the fiber axis.

• Repetitive Sequence: The sequence often repeats as Gly-Ala-Gly-Ala-Gly-Ser-Gly-Ala-Ala-Gly, with glycine and alanine or serine alternating.

• Mechanical Properties: The close-packed β-sheets provide strength, while interruptions allow for elasticity.

Example: The stacking of β-sheets in fibroin is stabilized by the interdigitation of alanine/serine and glycine side chains.

Collagen: Structure and Function

Properties and Organization

Collagen is the most abundant protein in vertebrates, forming the matrix of bone, tendons, and skin. Its unique triple-helical structure provides tensile strength and stability.

• Triple Helix: Collagen fibers are built from tropocollagen molecules, each consisting of three polypeptide chains (~1000 residues each) forming a left-handed helix, which wrap around each other in a right-handed sense.

• Amino Acid Composition: Rich in glycine and proline; every third residue is glycine. Contains hydroxyproline and hydroxylysine, which are important for stability.

• Sequence Motif: The repetitive motif is Gly-X-Y, where X is often proline and Y is proline or hydroxyproline.

• Hydrogen Bonding: Hydrogen bonds form between chains, stabilizing the triple helix.

Example: Collagen forms the matrix material in bone, providing a scaffold for mineral deposition.

Collagen-Related Disorders and Modifications

Collagen's function depends on post-translational modifications and cross-linking, which affect tissue strength and elasticity.

• Scurvy: A connective tissue disease caused by vitamin C deficiency, leading to impaired hydroxylation of proline and lysine, weakened collagen fibers, and reduced hydrogen bonding.

• Cross-Linking: Lysine side chains can oxidize to aldehyde derivatives, which react to form cross-links via aldol condensation and dehydration, making collagen less elastic and more brittle with age.

Example: The accumulation of cross-links in collagen over time contributes to the aging of connective tissues.

Collagen Synthesis and Assembly

Collagen biosynthesis involves multiple steps, some occurring in the endoplasmic reticulum and others extracellularly. Proper assembly and modification are essential for functional collagen fibers.

• Intracellular Steps: Synthesis and initial modifications occur in the endoplasmic reticulum.

• Extracellular Steps: Further processing and assembly into mature fibers occur outside the cell.

Additional info: Hydroxylation of proline and lysine residues requires vitamin C (ascorbic acid) as a cofactor.