Intermediate Filaments Flashcards
stucture of intermediate filaments
polymers
diameter of intermediate filaments
10nm
number of genes encode intermediate filaments
70 genes
polarity of intermediate filaments
intermediate filaments not polarized
overall structure of intermediate filament dimer: N-terminus to C-terminus
Nā -Head - Rod - Tail - Cā
domain of IF proteins conserved
rod domain
IF Nā and Cā domains makes the dimer:
polarized
structure of IF rod domain
alpha-helical, coiled-coil structure
alpha-helix in rod domain characterized by:
heptad repeat sequence
type of IF residues help back two proteins together
hydrophobic residues
IF rod domain has hydrophobic residues at positions:
hydrophobic residues at positions 1 and 4
fashion in which IF dimers associate with other dimers
anti-parallel fashion
tetramers symetric structure makes them:
not polar
basic building blocks of intermediate filaments
IF tetramers
forms when tetramers assemble end to end
protofilament
this forms when four protofilaments assemble
protofibril
four protofibrils assemble into:
10nm IF
number of interlocked protofilaments IF contains
16 protofilaments
number of protofilaments assemble into a protofibril
four protofilaments
number of protofibrils assemble into the 10nm IF
four protofibrils
IFs are more stable than:
microfilaments or microtubules
IFs are more stable than microfilaments or microtubules but are still:
dynamic
experiments proves dynamic nature of IFs: this labeled monomer injected into fibroblasts
keratin monomer injected into fibroblasts
IFs assemble and dissemble in order of:
hours
Class I intermediate filament protein type
acidic
Class I intermediate filament distribution
epithelial cells
Class II intermediate filament protein type
basic keratins
Class II intermediate filament distribution
epithelial cells
Class III intermediate filament protein type:
Desmin, GFP, vimentin
Class III intermediate filament distribution
muscle, glial cells, mesenchymal cells
Class IV intermediate filament protein type
neurofilaments
Class IV intermediate filament distribution
neurons
Class V interpediate filament protein type
laminins
Class V intermediate filament distribution
nucleus
IF disease: skin gets blistered
epidermolysis bullosa simplex
keratin 14 forms deterodimers with:
keratin 4
keratin 14 forms heterodimer with keratin 4 in:
basal cells of epidermis
keratin 14 and keratin 4 assemble into:
protofilaments
in mature cell keratin 4 and 14 replaced by:
keratin 1 and 10
epidermolysis bullosa simplex: keratin 14 and keratin 4 heterodimers cannot form tetramers or protofilaments when:
keratin 14 lacks N- or C- terminal domain
epidermolysis bullosa simplex: this lacks N- or C- terminal domain
keratin 14
epidermolysis bullosa simplex: these are fragile and unable to withstand abrasion
basal cells of epidermis
epidermolysis bullosa simplex: absence of K14/K4 protofilaments seperates:
epidermis from dermis
epidermolysis bullosa simplex: caused by epidermis seperating from dermis
blisters
IF disease caused by mutations in LMNA:
Hutchinson-Guilford progeria
Hutchinson-Guilford progeria caused by:
spontaneuous dominant mutations in Lamin A gene (LMNA)
Hutchinson-Guilford progeria: mutations in single base activates:
cryptic splice site
Hutchinson-Guilford progeria: mutation produces:
truncated Lamin A protein
truncated Lamin A protein called:
progerin
premature aging disorder
Hutchinson-Guilford progeria
S/S of Hutchinson-Guilford progeria:
baldness, pinched noses, aged skin, dwarfism, craniofacial defects
Hutchinson-Guilford progeria: cell part has abnormal morphology
nuclear membrane
Hutchinson-Guilford progeria: tissues with high levels of stress (like heart) undergo death due to:
nuclear instability
Lamin A synthesized as:
large precursor protein
Lamin A large precursor protein modified by addition of:
farnesyl group (lipid)
farnesyl modification common in proteins localized to:
membranes
cleaves Lamin A precursor at site of farnesyltation before release
Rce
Hutchinson-Guilford progeria: farnesyl modification last step being blocked leads to accumulation of intermediate in:
nuclei (which is cytotoxic
Hutchinson-Guilford progeria: farnesyl modification intermediate deforms:
nuclei
Hutchinson-Guilford progeria: type of drugs used to treat disease
farnesyl transferase inhibitors (FTIs)
