project study Flashcards
what is keratin
Keratin is a fibrous structural protein found in the cytoskeleton of epithelial cells. It forms strong intermediate filaments that give structure and mechanical strength to tissues like skin, hair, and nails. Keratin also plays a role in supporting the skin, healing wounds, and maintaining healthy nails and hair. It is a protective protein that’s less prone to scratching or tearing, helping epithelial tissues resist physical damage from friction or pressure.
keratin has a tripartite structure
Tripartite structure means something is made up of three distinct parts.
In the context of keratin, the tripartite structure refers to the three main regions of the protein:
Head (N-terminal) – non-helical, involved in filament interactions
Rod domain – α-helical, central region (~310 amino acids), essential for filament assembly
Tail (C-terminal) – non-helical, also important for interactions and stability
So, keratin’s tripartite structure just means it has these three functional sections that work together to form strong intermediate filaments
slide 1 photo
“This diagram shows how keratin intermediate filaments are assembled inside cells. At the bottom, we start with individual keratin proteins — Type I (acidic) and Type II (basic). These pair together to form a heterodimer, which is a coiled structure made of one of each type.”
“Next, two heterodimers line up in opposite directions and form a tetramer. This antiparallel arrangement helps give the filament flexibility and strength.”
“Multiple tetramers then pack side by side to form a unit length filament, which is like a short building block of the larger structure.”
“Finally, these unit-length filaments link end to end and twist together to create a 10 nanometer intermediate filament, which is the final keratin structure that gives cells — especially skin cells — the mechanical strength they need to resist stretching and tearing.”
how to explain slide 2 photo
(a) Monomer: The Basic Keratin Unit
The keratin protein begins as a monomer, with a central α-helical rod domain (shown in blue), flanked by non-helical N-terminal (NH₂) and C-terminal (COOH) domains.
This tripartite structure — head (NH₂), rod, and tail (COOH) — is critical for how keratins interact and align with one another.
The rod domain is responsible for forming the coiled-coil structure in the next step.
(b) Dimer: Coiled-Coil Formation
Two keratin monomers (one Type I and one Type II) wrap around each other to form a coiled-coil dimer.
They align in a parallel orientation — both NH₂ ends on one side and both COOH ends on the other.
This coiled-coil is stabilized by hydrophobic interactions along the helical regions.
This dimer is the fundamental building block of the filament.
(c) Tetramer: Staggered, Antiparallel Alignment
Two dimers come together in an antiparallel fashion — meaning the NH₂ end of one dimer aligns with the COOH end of another.
This creates a staggered tetramer, which is the smallest soluble subunit of the intermediate filament.
The sliding, staggered overlap of the dimers distributes mechanical stress evenly and adds flexibility to the final filament.
This antiparallel arrangement also neutralizes polarity, making intermediate filaments different from microtubules or actin filaments (which are polar).
(d) Protofilament: Lateral Assembly of Tetramers
Tetramers pack side-by-side, aligning laterally to form protofilaments.
These structures begin to resemble the growing filament. At this stage, there’s no twisting yet, but the width begins to increase.
(e) Mature Filament: Twisting into a 10 nm Structure
Finally, eight protofilaments twist together into a rope-like intermediate filament about 10 nanometers in diameter.
The helical twisting increases tensile strength, like the strands of a climbing rope.
The final filament is non-polar, flexible, and very strong, allowing epithelial cells to resist tearing during stretching or physical stress.
🔁 Summary of Functional Importance:
The NH₂ and COOH terminals allow keratins to orient and stabilize interactions.
The staggered alignment and twisting allow the filament to absorb and distribute mechanical forces, which is essential for tissues like skin, where cells are constantly stressed.
Any mutations that interfere with coiled-coil formation, tetramer alignment, or filament twisting (e.g., in the 1A, 2B, or linker domains) can weaken the entire structure — leading to diseases like Epidermolysis Bullosa Simplex (EBS).
Keratin Defects in EBS
K14 (Type I) and K5 (Type II) always function together as a heterodimer pair in basal keratinocytes (the deepest layer of the epidermis).
For proper filament formation, you need both proteins to be fully functional.
A mutation in either KRT14 or KRT5 will disrupt the entire filament network, even if the other partner is normal.
So:
Mutations in K14 → lead to misfolded or unstable filaments
Mutations in K5 → same outcome — filament collapse and cell fragility
Either one → causes basal layer cytolysis, resulting in the blistering symptoms of EBS
Some subtypes of EBS (like Dowling-Meara) are more strongly associated with K14 mutations.
Other cases, especially milder forms, can be caused by K5 mutations.
more about keratin in ebs
In EBS, mutations affect key structural regions K15 and K14:
The 1A and 2B rod segments
The L12 linker
The H1 domain (for K5)
These regions are needed for filament assembly and stability.
Mutant keratins still pair with normal keratins, but the resulting filaments are weak or unstable.
This weakens the cytoskeleton, making the cells prone to breaking even from gentle friction.
In severe cases (e.g., EBS), keratins clump abnormally in the cell, visible by electron microscopy.
second photo explanation
Top Graph (a): Buckling Wavelength
“This graph compares the buckling wavelength of intermediate filaments formed by wild-type K14 (blue) and the mutant K14 R125P (light tan). Buckling wavelength gives us insight into filament flexibility and mechanical properties. Although the values are similar, the mutant filaments may still be functionally impaired in how they respond to stress inside cells.”
🔹 Bottom Images (b & c): Filament Organization
“Here we see fluorescent images of cells expressing wild-type K14 (left) and mutant K14 (right). In the wild-type cells, the keratin intermediate filaments form a clear, organized network around the cell periphery — this is how keratin normally stabilizes the cell.”
“But in the mutant cells (R125P), the keratin filaments are disorganized and more diffuse, which shows us that the mutation disrupts normal filament assembly and structure. This kind of structural failure makes the cytoskeleton weaker and contributes to the cell fragility and blistering seen in EBS.”
keratin
Keratin is a type of intermediate filament protein.
Specifically found in epithelial cells (like skin, hair, nails, etc.)
Intermediate filaments are one of the three major components of the cytoskeleton, alongside:
Microfilaments (actin)
Microtubules (tubulin)
Intermediate filaments (like keratin)
So yes — keratin forms intermediate filaments, and those filaments are a critical part of the cytoskeleton in epithelial cells.
🧠 What That Means:
Keratin → Intermediate Filaments → Cytoskeleton
Keratin proteins (like K5 and K14) assemble into intermediate filaments, which:
Give the cell mechanical strength
Help anchor cell junctions
Maintain cell shape and stability
These filaments form a network in the cytoplasm and help protect cells from stretching or mechanical stress.
