10: Protein Filaments & Cytoskeleton Flashcards
(47 cards)
Types of protein assemblies with symmetry?
2
Oligomeric symmetrical assemblies include:
dimers (with 2 fold sym)
ring structures
Protein Assemblies and Symmetry
2
they have point group symmetry
> keep at least one point fixed with symmetrical elements that pass through it
> cyclic, dihedral, tetrahedral, octahedral, isosahedral
Protein Assemblies without symmetry?
e.g.
packed sheets/flat surfaces
> 2D/3D Crystals can form hexagonally packed sheets
or tubes
Protein Filaments: what are they
Protein filaments are helical polymers formed by the repeated assembly of protein subunits, allowing them to grow indefinitely without a defined maximum size.
Protein Filament
3 structures + examples
Filament Helix
Composed of multiple protein subunits arranged per helical turn
Usually has an unfilled or empty central core
Does not form an enclosed wall or tube
Example: Actin filaments
Fiber Helix
Densely packed protein subunits
No hollow core; solid throughout
Rope-like or cable-like structure
Example: Intermediate filaments
Hollow Tube
Cylindrical, tube-like structure
Composed of protofilaments arranged in a circular pattern
Has a hollow central lumen (core)
Example: Microtubules
Protein Filament
parameters?
6
same as helical parameters:
Pitch: change in length/turn
Rise: Length/Subunit
Helical Radius
Twist (per subunit)
Units per turn
Handedness
What are the basic dynamics of filament formation?
- Nucleation
> Lag phase until nucleation - Growth
> prop. to [subunits] - Steady state
> no net change in polymer
Kon and Koff
and how are they related to Steady State
Kon = Rate of subunit association
> prop. to Conc/1st order
Koff = Rate of subunit disassociation
> 0. order
SS is when
Kon*C = Koff
> without net change in length
> C = critical concentration
Nucleation defined
Critical step in filament formation (as well as for protein crystallisation)
> after this the growth of protein is prop. to number of free subunits
Collagen Fibres
3
what is it, how is it prod, role?
> Major component of EZ Matrix
prod. and sek. by fibroblasts
bear mechanical strength to connective tissues
Filamentous Proteins:
Basic Fibres examples (2)
Complex Filaments (3)
Basic:
Collagen
Amyloid Plaques
Complex:
Cytoskelett filaments:
> Actin, Microtubules, Intermediate filaments
Collagen structure:
50nm diameter in collagen fibril
> made up of collagen triple helix with diameter of 1.5nm
Collagen Triple Helix
structure?
sequence?
+ 3
tightly packed triple helix with 3 residue repeat!!
> Glycine - Proline - Hyp
Glycine is 100%/strictly conserved and first in sequence
> important for tight packing
Hyp is generated post TL (Proline-Hyp)
Proline pref. 2nd and Hyp prefer 3rd in sequence
Collagen types?
there exists diff types of collagens with different roles and tissue expression
the repeat element is conserved through evolution
> through gene duplication
and then there’s variable non repeat regions
Amyloid Filaments
association?
2
usually with neurodegenerative diseases
Abeta = Alzheimers disease
PrP = Spongiform Encephalopathies (braine)
What is the organization of ALL amyloid fibrils?
Cross-beta-sheet motif w/ Parallel beta sheets !!!
Polymorphic amyloid cores
> leads to variable structure: 2-layer and 3-layer structures
Cross-beta-sheet commonly surrounded by undefined peripheral domains
What is the process of amyloid formation?
- Native protein must first be unfolded to turn into Amyloid !!
- Oligomer Nucleation (Lag phase)
- Growth
- Amyloid Fibril
> at any point there can be rescue pathways to turn back into the folded protein form
Amyloid formation competition?
directly in competition with folded protein
> Amyloid fibril = Stable but has high Ea
unfavoured kinetics !!
unfavoured activation steps !! which favours non amyloid aggregates are they’re easier to degrade
Prion diseases ?
Proteins in abnormal states which induce/stabilise protein misfolding
> they act as templates to convert normal proteins into misfolded conformation
= chain react. eventually leads to amyloid fibrils
> they themself are made after rare conf. change (2 steps)
Human prion protein filaments are called?
PrP
> major component of amyloid fibrils as shown by labelling experiments
PrP structure
normal and abnormal
Normal PrP = Mix of alpha and beta
> 3 alpha
> 2 beta
Abnormal PrP
> N-terminal unfoldes and refolds into different conformation
> can form extended filaments
Prion smaller aggregates vs Fibrils
smaller aggregates: dimers/trimers, Oligomers, filaments
> biologically active and neurodegenerative
Larger/Fibrils:
> may be less harmful HOWEVER they spont. release smaller aggregates
> can be rescued by ATP-deaggerases or they will accumulate
Cytoskeleton Overview:
Microtubules across cell
Actin filaments at edge
(in cells)
Actin:
about it?
ATP/forms?
polarity?
diameter?
40kDa protein
Monumeric form: G-Actin: ATP-bound
ATP-ADP upon polymerisation to F-actin
> Interwined helical filaments: F-actin (bound to ADP)
diameter: 7nm
Polar:
+ (monomers prefer to add here)
- (monomers prefer to disassociate here)
