Collagen Structure and Function Flashcards
other ECM components are utilized in particular tissues according to other desired properties, such as (3)
regulation of assembly of other ECM proteins
binding of growth factors
regulation of mineralization
types of fibrous proteins (2)
structural
adhesive
structural fibrous porteins
provide…
examples (3)
provide tensile strength and elasticity
collagen, elastin, fibrillins
adhesive fibrous proteins
help cells…
examples (3)
help cells attach to ECM
fibronectin, vitronectin, laminin
glycosaminoglycans (GAGs)
long polysaccharides consisting of repeating disaccharide units
GAGS are often covalently linked to protein in the form of —
proteoglycans
proteoglycans form hydrated gel in which — proteins embed- resits — and aqueous phase permits — of nutrients)
fibrous
compression
diffusion
major structural component of ECM
collagen
collagen is –% of total protein mass in mammals
–% of organic material in bone, dentin
25%
90%
what kind of molecule is collagen
trimeric molecules consisting of three identical (homotrimeric) or non-identical (heterotrimeric) polypeptide chains (alpha chains)
what are collagen molecules characterized by
long, stiff triple stranded helical structure with 3 alpha-chains wound around each other in a rope like superhelix
all collagen molecules contain at least one…
triple helical region (collagenous domain)
the collagenous domain requires the presence of — every third amino acid
glycine
usually fly-X-Y, where X is often proline and Y is often 4-hydroxyproline
– different collagens identified, encoded by up to – different genes
28
42
how are collagen divided? (2)
fibrillar
non-fibrillar
polypeptide nomenclature
alpha chain numbering, collagen type
a1(2)
gene nomenclature
collagen type, alpha chain numbering
COL2A1
major fibrillar collagens (3)
1
2
3
fibrillar collagens are large collagenous domains of ~—- amino acids
~1000
assemble into higher order (polymeric) rod like structures called
collagen fibrils
molecules arranged with quarter-staggered carry gives
characteristic banding
after fibrils form, they are crosslinked between — of adjacent molecules, which
lysine
greatly increases tensile strength
type 1 collagen
principal collagen found in tendon, bone, ligaments, dentin, skin, (occurs in ECM as elongated fibrils)
type 2 collagen
principal collagen in cartilage matrix
type 3 collagen
(with five) important in dermal reticular fibers (small amounts in dentin)
type 5 collagen
associated with type 1 (may regulate assembly of heterotypic fibers containing type 1 and type 5)
type 11 collagen
found in cartilage, eye. helps regulate spacing/diameter of type 2 collagen fibrils
type 1 collagen is the major structural component of (7)
bone skin tendon teeth periodontal ligament dermis fasciae
collagen is –% of organic material in bone and teeth
90%
type 1 collagen is a heterodimer of
two alpha1 chains and one alpha2 chain encoded by two separate genes, COL1A1 and COL1A2
mutations in type 1 collagen genes (COL1A1 and COL1A2) are associated with
osteogenesis imperfecta
different variations of organization of type 1 collagen fibrils (5)
parallel bundles (tendons, ligaments) orthogonal lattices (cornea), plywood like layers concentric weaves (bone) wickerwork pattern, resists tensile stress in multiple directions (skin) fibrils arranged in sailing pattern around dentinal tubules (teeth)
type 2 collagen is the major fibrillar collagen in (3)
cartilage
vitreous humor
inner ear
type 2 collagen is a homotrimer of..
alpha1 chains encoded by COL2A1 gene
mutations in type 2 collagen cause
chondrodyplasias
differences between non fibrillar and fibrillar collagen (3)
triple helical domains are shorter
interrupted by non collagenous sequences
structure is less rigid/more flexible
type 4 and 6 non fibrillar cartilage play an important role in
basal lamina
type 7 non fibrillar cartilage is a key component in
anchoring fibrils that attach epithelia to underlying connective tissue
type 9 non fibrillar cartilage may regulate assembly of
type 2 collagen fibrils
type 10 non fibrillar cartilage is highly expressed in
growth plate hypertrophic cartilage
steps of collagen biosynthesis/assembly (8)
synthesis of pro-alpha chain hydroxylation of selected prolines and lysines glycosylation of selected hydroxylysines self assembly of three pre-alpha chains pro collagen triple helix formation secretion cleavage of pro peptides self assembly into fibril
primary animo acids in collagen fibers (3)
glycine
proline
hydroxyproline
hydroxylysines and hydroxyprolines are relatively rare in
other animal proteins
secondary structure of collagen alpha polypeptide chains
extended left handed helix (collagen helix)
proline confers 60 degree twist in molecules, which disrupts
other types of secondary structure from forming (ex. alpha helices, beta sheets, etc)
each collagen helix is stabilized by
static revision of pyrrolidone rings of proline dn hydroxyproline residues
collagen tertiary structure
no tertiary structure (3D structure of single protein molecule)
aka no folding on individual polypeptide chains due to intrachain S-S bonding, hydrophobicity, hydrogen bonding, etc
collagen quaternary structure (3D structure of multi subunit protein)
three identical alpha chains wind around each other to form a right handed triple helix (3 aa residues per turn)
For each Gly-X-Y, a hydrogen bond forms between
the amide hydrogen of a glycine in one chain and carbonyl oxygen of residue X in an adjacent chain
Hydrogen bonding also occurs between OH
groups and
amide groups of residues in adjacent chains
Hydrogen bonding also occurs between OH
groups and amide groups of residues in adjacent chains, which stabilizes..
triple helix of collagen
Makes sense that glycine occupies every 3rd position because
it has the least
bulky side chain (there isn’t much room inside the triple helix)
Because there are 3 residues per turn of the helix, every 3rd residue must
be glycine, which allows
three helical alpha chains to pack together to form a
triple helix
Amino acids in X and Y positions (e.g. proline, 4-hydroxyproline) are on
the
outside because there is room for their bulkier side chains
key steps in collagen biosynthesis and assembly (3)
post translational modifications (hydroxylation, glycosylation, intrachain disulphide bonding)
post translational modifications (proteolytic processing of pro collagen)
collagen crosslinking
post translational modifications of collagen are important in its (2)
biosynthesis and assembly
collagens undergo extensive post translational modifications in the ___ prior to triple helix formation
ER
several enzymes/molecular chaperones assist in
trimerization and folding
Prolyl hydroxylases and lysyl
hydroxylase –
hydroxylates
selected prolines and lysines
(requires vitamin C as cofactor)
FKBP10
(peptidyl prolyl cis-trans
isomerase) – accelerates protein
folding
Collagen glycosyltransfer-
ases –
glycosylates selected
hydroxylysines
Protein disulphide isomerase
(PDI) –
catalyzes formation of interchain disulphide bonds between cysteines during nucleation of three polypeptide chains at C-terminus
Hsp47 –
chaperone protein that
binds to disulfide bonded collagen
trimers and helps complete formation
of the triple helix
proteolytic processing of pro collagen molecules in important for — formation
fibril
C-propeptides are important
in nucleation of three
collagen chains to form a
collagen trimer
fibril formation only occurs after C and N propeptides are removed to form
tropocollagen
collagen fibril assembly forms a — — array
quarter staggered
collagen — stabilizes the fibers
crosslinking
Strength of collagen fibrils greatly increased by
covalent
crosslinking between lysines of adjacent molecules
key enzymes of cross linking
Lysol oxidases (5 identified)
Inhibition of crosslinking (2)
reduces tensile strength of
fibrils/ increases tissue fragility
Amount of cross linking increases with
aging
what collagen is the major ECM component of dentin, cementum, periodontal ligament?
type 1 collagen
enamel is the only calcified tissue that does not contain
abundant collagen
collagen in periodontal ligament attaches
cementum layer of tooth root to alveolar bone
gingiva also contains abundant collagen fibers to
attach gingiva to tooth and alveolar bone
Functions of collagen fibers in the
gingiva (2)
− Anchoring gingival tissue to tooth/
alveolar bone
− Resisting masticatory forces
collagen fibers in gingiva classified into
five groups
dentinogingival/alveogingival
circumferential
periosteal
transseptal
Dentinogingival/Alveogingival =
calcified into cementum/bone at one end,
free at other end. Hold free gingiva
against tooth
Circumferential=
encircle tooth
Periosteal=
hold attached gingiva
against bone
Transseptal=
run between teeth (not
visable in figure)
Periodontal ligament composed
mainly of bundles of
type I
collagen fibrils
PL also also contains — fibers
composed of fibrillin (provides
elasticity for tooth movement)
oxytalan
Sharpey’s fibers
portion of fibrils anchored into
mineralized cementum or bone
Fibrils classified into five groups
based on
anatomical location
major ECM component of dentin (~90%
of organic matrix)
Collagen
what collagen is mainly found in dentin
type 1, with trace amounts of type 3 and 5
type 4 and 7 collagen are found in the enamel organic matrix at the
DEJ
Type IV collagen restricted to
narrow zone at the DEJ
Type VII collagen found in enamel organic matrix
adjacent to DEJ
- fibers surround enamel rods
Type VII may play a role in attachment of enamel to
underlying dentin
— — underlies all epithelial cell layers (synthesized by cells
resting on it)
Basal lamina
what does the basal lamina separate
epithelium from underlying connective tissue stroma
how thick is the basal lamina
40-120 nm thick
In kidney glomerulus basal lamina it is important in determining which molecules will pass into
urine from blood (glomerular filtration)
in skin, basal lamina is critical for attaching epidermis (epithelial outer
layer) to
dermis
In oral mucosa, basal lamina is critical for attaching epithelium to
lamina propria
Other roles of basal lamina in addition to structural/filtration (3)
- Determining cell polarity
- Influencing cell metabolism
- Regulating cell survival, proliferation, migration, differentiation
key components of the basal lamina
glycoproteins (laminin, nidogen)
collagens (type 4 collagen)
proteoglycans (perlecan (proteoglycan))
here are six genes encoding type 4
collagen alpha chains –
COL4A1, COL4A2, COL4A3, COL4A4,
COL4A5, COL4A6
how many different heterotrimers can be formed from type 4 collagen
3
α1 α1 α2) (α3 α4 α5) (α5 α5 α6
Type VII collagen forms
anchoring fibrils
Type VII collagen forms anchoring fibrils - interacts with type I collagen in stroma and type IV collagen/ laminin in basal lamina to form the
basement membrane
important function in anchoring epidermis to underlying dermis or epithelium to underlying
stroma
inherited disease dystrophic epidermis bullosa due to mutations in
COL7A1
dystrophic epidermis bullosa
disease results in very fragile skin/mucous membranes that blister easily and can be sloughed off, problems with lining of the oesophagus, etc.
