Intermediate filaments Flashcards
Give some characteristics of IF.
It is resistant to everything apart from UREA (denaturant) but it can reassemble in the right conditions (on removal of denaturant)
Withstands large strains without tearing; it has the greatest deforming force.
Present throughout whole cell right to membrane.
APOLAR
Secondary structure of alpha helical coils is conserved. Heptad repeats in -helices: form coiled coils and sequence motifs at either end of rod domain important in assembly
No energy required
It has a multigene family and displays specific expression patterns depending on the cell type. (different functions/different tissues)
List some types of IF.
1) Nuclear (in the lamina of the inner nuclear envelope)
2) Vimentin (muscle, glial schwann cells)
3) Epithelial (skin, hair, nails)
4) Axonal (neurone long and thin but strong)
What are the 5 major classes of IF?
Classes are large families of proteins showing multigene origin (65 genes)
Different filament networks can coexist in the same cell (keratin and vitentin coexist)
1) Acidic keratin 1-8
2) Basic keratin 9-20
Both in epithelial cells
3) Desmin/vitenin (connective tissue)
4) Neurofilaments
5) Lamins (all nucleii)
What is the structure if IF?
GLOBULAR HEAD AND TAIL DOMAINS ON EITHER SIDE OF THE MIDDLE ALPHA HELICAL ROD DOMAIN.
head is essential for assembly (helped by tail domain)
rod domain becomes coiled-coil dimer then a staggered TETRAMER of about 30-65nm.
8 tetramers hen form a FILAMENT is a like a rope.
Subunits can be exchanged
What are the heptad repeat in the alpha helix role?
It is needed for dimerisation (coiled coil formation)
Describe the manner in which the IF arise.
no ATP/GTP, cofactors or associated proteins required for the IF to POLYMERISE SPONTANEOUSLY.
Keratin intermediate filament proteins have different properties.
Type 1: Acidic isoelectric points but type 2 had neutral
Type 1 has a lower molecular weight then Type 2.
However they are both heteropolymers
Describe Specific paired expression of type 1 and 2 keratins in tissues
The two families HAVE TO interact for different polymers to be formed in particular tissues; keratin distrubution tied to the differentiation of cells.
This has to be in the same quantity of each family (1:1)
For example K4 and K12 form a filament together.
K7&8 with K18&20.
BUT some keratins will never interact with eachother (eg, K1 and K18) in the SAME filament.
Keratin meshwork consistant, distribution is stable.
Give examples of Intermediate filament attachment sites/junctions between cells.
KERATINS
Desmosomes (link cell to cell)
Hemidesomosomes
Type III IF proteins
- Desmosomes - GFAP/Desmin
- Ankyrin - plasma membrane
What diseases can be caused by mutations in basal cell keratins K5 or K14?
Epidermolysis bullosa simplex (blistering of the skin) where keratin formation is defected and cells arent properly connected by networks (gaps in epithelium.
Describe the location of Desmin (Class3)
It surrounds the sarcomere in skeletal muscle; connecting to the Z line and M line
Describe the structure of Lamins, (Class 5) in nuclei
There is a LONG C TERMINAL tail (with the nuclear localisation signal that dock with nuclear pores/membranes)
In addition, the 1B helix contains extra;-helical/coiled coils ~ 55nm long (~350 amino acids): longer than cytoplasmic rod domains.
The difference in length means lamins cannot co assemble with other filaments
Phosphorylation allows (re)disassembly. when needed in mitosis
Overall form a meshwork
Describe the structure of Neurofilaments (class4)
Type NF-H: It has a very long repeat in the tail domain of KSP. This allows for CROSS BRIDGING to occur giving an even stronger structure.
(NH-F lacks this long repeat tail)
