Collagen structure and function 1 Flashcards
What space is filled with a network of large macromolecules?
Extracellular Matrix
What are specialized tissues in which ECM is more abundant than cells?
connective tissues
What types of oral and craniofacial tissues involve the ECM?
- teeth/bone
- cartilage
- lamina propria
- gingiva/periodontium
What is a stroma?
cells embedded in matrix
What are the major components of stormal matrix?
collagen embedded in polysaccharide ground substance of hyaluronan and proteoglycans
What cells secrete ECM in most connective tissues?
fibroblasts
What is the specialized matrix at the interface between connective tissues stroma and epithelium?
basal lamina
what type of collagen tethers the basal lamina to the CT?
type VII
basement membrane is comprised of what?
basal lamina and layer of collagen fibrils
What is the function of the ECM in bone?
- Support and locomotion
- Calcium homeostasis
- Skeleton protects brain, internal organs
What is the function of ECM in teeth?
- Provides strength/structure to tooth
- Resists shear and compression forces associated with chewing
What is the function of ECM in cartilage?
- Support and locomotion
- Resilient - shock absorber for compressive forces associated with locomotion, mastication etc.
what are the roles of ECM not related to structure?
-embryonic development
-regulation of cell function
-tissue repair/wound healing
-angiogenesis
The composition of ECM in each tissue is perfectly suited to ______________________
biomechanical/functional requirements of the tissue
what are the ECM components?
-collagen
-proteoglycans
-elastin
-fibrillin-1
-mineral
What property does collagen have?
tensile strength
What property does proteoglycans?
resilience/resistance to compression
What property does elastin have?
elasticity/resilience
What property does fibrillin-1 have?
controlled elasticity
What property does mineral have?
strength, hardness, brittleness
What are examples of structural fibrous proteins?
collagen, elastin, fibrillins
What are examples of adhesive fibrous proteins?
fibronectin, vitronectin, laminin
28 different collagens identified, encoded by up to _____ different genes
42
All collagen molecules contain at least one ___________
triple helical region associated with glycine every third amino acid
What is the major structural component of ECM?
collagens
What are collagens structure?
trimeric molecules consisting of three identical or non-identical polypeptide chains
(long, stiff triple stranded helical structure with 3 a-chains wound around each other like a rope)
What are the major fibrillar collagens?
I, II, III
what are fibrils crosslinked between?
lysines of adjacent molecules
Which collagen type is found in tendon, bone, ligaments, dentin, skin?
Type I
Which collagen type is found in cartilage matrix?
Type II
What is the Type I collagen structure?
heterotrimer of two a1(I) chains and one a2(I) chain (genes COL1A1 and COL1A2)
mutations in type I collagen genes (COL1A1 and COL1A2) are associated with what?
osteogenesis imperfecta
What are the ways in which type I collagen fibrils vary in 3D arrays?
- parallel bundles (tendons/ligaments)
- orthogonal lattices (cornea)
- concentric weaves (bone)
- wickerwork pattern (skin)
- swirling pattern (teeth)
What is the major collagen type in cartilage, vitreous humor (eye), and inner ear?
Type II
What is the structure of Type II collagen?
homotrimer of a1(II) chain (COL2A1)
What do mutations in type II collagen cause?
chondrodysplasias
structure of non-fibrillar collagen
triple helical domains shorter, interrupted by non-collagenous sequences-structure less rigid and more flexible
What collagen types are important in basal lamina?
Type IV and VI
What collagen type is key in anchoring fibrils that attach epithelia to underlying connective tissue?
Type VII
In collagenous domains ______ is present every 3rd residue?
glycine (Gly-X-Y motif)
what is the X in Gly-X-Y motif most commonly?
proline
what is the Y in Gly-X-Y motif most commonly?
4-hydroxyproline
is the collagen helix left or right-handed?
left-handed
How is the collagen helix stabilized?
by static repulsion of pyrrolidone rings or proline and hydroxyproline residues
Which amino acid has a 60 degree twist?
proline (disrupts other structures from forming beside a helix)
What type of helix forms from 3 procollagen chains?
collagen right handed triple helix (quaternary structure)
Which amino acid has the least bulky side chain?
glycine
what stabilizes the triple helix of collagen?
hydrogen bonds
Why is every 3rd residue glycine?
allows three helical alpha chains to pack together to form a triple helix
What are some key steps in collagen biosynthesis and assembly?
- post translational modifications
- collagen crosslinking
what are the post-translational modifications in collagen biosynthesis and assembly?
hydroxylation
glycosylation
protolytic processing of procollagen
Where do collagens undergo extensive post translational modifications?
ER
What does the post-translational modification prolyl hydroxylases and lysyl hydroxylase do?
hydroxylates prolines and lysines (needs vitamin C)
What does the post-translational modification FKBP10 do?
accelerates protein folding
What does the post-translational modification collagen glycosyltransferasesd do?
glycosylates selected hydroxylysines
What does the post-translational modification protein disulphide isomerase (PDI) do?
catalyzes formation of interchain disulphide bonds between cysteines
What does the post-translational modification Hsp47 do?
chaperone protein that binds to disulfide bonded collagen trimers
What does the procollagen processing ADAMTS2, 3, 14 do?
N-proteases resonsible for cleaving off N-propeptide
What does the procollagen processing BMP-1/tolloid proteinases do?
C-proteinase responsible for cleaving off C-propeptide
The amount of crosslinking of collagen __________ with age
increases
What is the key enzyme in collagen crosslinking with fibrils?
lysyl oxidases
What is the major ECM component of dentin, cementum, and periodontal ligament?
Type I collagen
What is the only calcified tissue that does not contain abundant collagen?
enamel
what attaches the cementum layer of tooth root to alveolar bone?
collagen in PDL
what attaches the gingiva to tooth and alveolar bone?
abundant collagen fibers in gingiva
What are the five groups of collagen fibers in gingiva?
- Dentinogingival and Alveogingival (calcified into cementum/bone at one end, free at other end)
- Circumferential (encircle tooth)
- Periosteal (hold attached gingiva
against bone) - Transseptal (run between teeth)
What is the portion of fibrils anchored into mineralized cementum or bone?
sharpey’s fibers
What type of collagen in dentin?
Type I with trace amounts of III and V
What type of collagen in enamel organic matrix at the DEJ?
Type IV and VII
What collagen type is important in basal lamina?
Type IV
What is the function of basal lamina in kidney glomerulus?
determines which molecules will pass into urine from blood
What is the function of basal lamina in skin?
attaches epidermis to dermis
What is the function of basal lamina in oral mucosa?
attaches epithelium to lamina propria
What are the key components of basal lamina?
glycoproteins
collagens (Type IV collagen)
proteoglycans
What mutation and collagen type is involved in dystrophic epidermis bullosa?
COL7A1
Type VII