Lecture 40 Collagen Structure and Function Flashcards
1
Q
What is the extracellular matrix?
A
- composed from large repertoire of specialized ECM proteins with various properties assembled into an organized network/meshwork
- often in close association with producer cells
2
Q
What are connective tissues?
A
- specialized tissues in which ECM is more abundant than cells
3
Q
What is the laminal propria beneath oral epithelium composed of?
A
- composed of collagen fibers in a connective tissue or stromal matrix
4
Q
Teeth/bone
A
- specialized mineralized connective tissues
5
Q
Gingiva, peridontium
A
- have a stromal matrix containing collagen
6
Q
What is cartilage?
A
- proteoglycan-rich specialized connective tissue
7
Q
What are stroma?
A
- cells embedded in matrix
8
Q
What are the major components of stromal matrix?
A
- collagen embedded in polysaccharide ground substance of hyaluronan + proteoglycans/glycosaminoglycans
9
Q
Where are stromal cells derived from?
A
- derived from mesodermal lineage
10
Q
What secretes ECM in most connective tissue?
A
- fibroblasts
11
Q
What other cells have the capability to secrete ECM?
A
- fibroblast related cells
- (osteoblasts, chondrocytes, odontoblasts)
12
Q
What is the Basal Lamina?
A
- specialized matrix at interface between connective tissue stroma and epithelium
13
Q
What tethers lamina to underlying connective tissue?
A
- type VII collagen anchoring fibrils
14
Q
What is the “basement membrane”?
A
- basal lamina combined with layer of collagen fibrils
15
Q
How is ECM traditionally viewed?
A
- traditionally viewed as a structurally stable material whose function is to provide support/anchorage to cells and tissues/demarcate boundaries between cells/tissues
16
Q
ECM function in bone
A
- support and locomotion
- calcium homeostasis ( reservoir of calcium to be released)
- protects brain and internal organs
17
Q
ECM function in teeth
A
- provides strength/structure to tooth
- resists shear and compression forces associated with chewing
18
Q
ECM function in cartilage
A
- support and locomotion
- resilient - shock absorber for compressive forces associated with locomotion, mastication
19
Q
`ECM roles in addition to structural roles
A
- Embryonic development (cell adhesion/migration/tissue morphogenesis)
- Regulation of Cell function (signaling/ growth/ differentiation)
- Tissue repair/ wound healing
- Angiogenesis
20
Q
How does the composition of ECM change in each tissue?
A
- perfectly suited to biomechanical/functional requirements of the tissue
21
Q
How is ECM viewed as composite material?
A
- various building materials (macromolecules) with different mechanical properties combined/organized to create a tissue with optimal mechanical properties
22
Q
What encodes for the components of ECM?
A
- genes
23
Q
what is the EcM like in the bone and teeth?
A
- calcified hard ECM
24
Q
What is the ECM like in the cornea?
A
- optically transparent ECM
25
What is the composition of ECM in tendons?
- rope-like organization of collagen gives tensile strength in one direction
26
What is the property of collagen (fibrillar)?
- tensile strength
27
What is the property of proteoglycans?
- resilience/resistance to compression
28
What is the property of elastin?
- elasticity/resilience
29
What is the property of Fibrillin-1 (microfibrils)?
- controlled elasticity
30
What is the property of the mineral hydroxyapatite?
- strength, hardness, but also brittleness
31
What are the major macromolecules of the ECM?
- Fibrous proteins
| - Glycosaminoglycans (GAGs)
32
What are the structural fibrous proteins?
- collagen, elastin, fibrillins
| provide tensile strength, elasticity, etc.
33
What are the adhesive fibrous proteins?
- fibronection, vitronectin, laminin
(help cells attach to ECM)
(have receptors on cell surface)
34
______ are long polysaccharides consisting of repeating disaccharide units often covalently linked to protein in the form of proteoglycans (form hydrated gel in which fibrous proteins embed- resists compression and aqueous phase permits diffusion of nutrients etc)
- Glycosaminoglycans (GAGs)
35
_____ is the major structural component of ECM (25% of total protein mass in mammals) (90% of organic material in bone, dentin)
- collagen
36
How many chains does collagen consist of?
- 3 poly peptide chains (alpha chains)
37
Are the collagen chains homotrimeric or heterotrimeric
- they can be either
38
T/F all collagen molecules contain at least one triple helical region (collagenous domain) - requires presence of glycine every third amino acid ( usually gly-X-Y where X is often proline and Y is often 4-hydroxyproline)
- True
39
Is type 2 collagen a homo or hetero trimer?
- homo trimer that has 3 alpha 1 chains
40
is type 1 collagen a homo or hetero trimer?
- its a hetero trimer with 2 alpha 1 chains and one alpha 2 chains
41
What chains make up type 6 collagen?
- alpha 1, 2, and 3
| - type 6 is heterotrimer
42
What type of collagen assembles into higher order rod-like structures?
- fibrillar collagens
43
What are the fibrillar collagens?
- 1
- 2
- 3
- 5
- 11
- 24
- 27
44
What are the major fibrillar collagens?
I, II, III
45
After fibrils form they are ________ between lysines of adjacent molecules (greatly increases tensile strength)
- Crosslinked
46
What gives fibrillar collagen its characteristic banding?
- the molecules are arranged with quarter- staggered array
47
What is the principle collagen found in tendon, bone, ligaments, dentin, skin
- Type I
| occurs in ECM as elongated fibrils
48
T/F Functions of Fibrillar collagens are relevant to craniofacial biology
- T
49
What is the principle collagen in cartilage matrix?
- type II
50
What type of collagen (with V) is important in dermal reticular fibers (small amounts in dentin)
- type 3
51
What type of collagen is associated with type I (may regulate assembly of heterotypic fibers containing type I and type V)?
- type V
52
What type of collagen is found in cartilage, eye, and helps regulate spacing/diameter of type II collagen fibrils
- type XI
53
What is the major structural component of bone, skin, tendon, teeth, periodontal ligament, dermis, and fasciae?
- type I collagen
54
What makes up 90% of organic material in bone and teeth?
- type I collagen
55
What types of chains make up Type I collagen?
- heterotrimer of two alpha i chains and one alpha 2 chain encoded by genes COL1A1 and COL1A2
56
What do mutations in type 1 collagen genes lead to?
- osteogenesis imperfecta
57
How are the type 1 collagen fibers in the tendons/ligaments arranged?
- parallel bundles
58
How are the collagen of the cornea arranged?
- orthogonal lattices (ply-wood like layers)
| - this is transparent so you can see
59
What is the arrangement of type 1 collagen in bone?
- concentric weaves
60
Why is the collagen of the skin arranged in wickerwork pattern?
- resists tensile stress in multiple directions
61
How is the collagen in the teeth arranged?
- fibrils arranged in a swirling pattern around dentinal tubules
62
What is the major fibrillar collagen in cartilage, vitreous humor, and inner ear?
- type II collagen
63
What is the chain composition of type II collagen?
- homotrimer of two alpha 1 chains encoded by COL2A1
64
What do mutations in type II collagen cause?
- chondroplasias
65
What are the non fibrillar collagens?
- IV, VI-X, XII- XXIII, XXV, XXVI, XXVIII
66
How are non fibrillar collagens arranged?
- they are triple helical domains that are shorter, interrupted by non-collagenous sequences ->
- structure is less rigid and more flexibile
67
What non fibrillar collagens have an important role in basement membrane?
- IV and VI
68
What no fibrillar collagen is a key component of anchoring fibrils that attach epithelia to underlying connective tissue
- type VII
69
What collagen may regulate assembly of type II collagen fibrils?
- type IX
70
What collagen is highly expressed in growth plate hypertrophic cartilage?
- type X
71
_______ is the major ECM component of Dentin, Cementum, and Peridontal ligament
- Type I collagen
72
_______ is the only calcified tissue that does not contain abundant collagen?
- Enamel
73
Collagen in the ______ attaches cementum layer of tooth root to alveolar bone
- peridontal ligament
74
_____ also contains abundant collagen fibers to attach gingiva to tooth and alveolar bone
- Gingiva
75
What are the functions of collagen fibers in the gingiva?
- anchoring gingival tissue to tooth/alveolar bone
| - resisting masticatory forces
76
______ collagen fibers are calcified into cementum/bone at one end and free at the other end, and hold free gingiva against the tooth
- Dentinogingival/ Alveogingival
77
________ encircle the tooth
- circumferential collagen fibers
78
_____ hold attached gingiva against bone
- periosteal
79
_____ run between teeth
- transseptal
80
What type of collagen fibrils is the peridontal ligament primarily composed of?
- Type I
81
What provides elasticity in the periodontal ligament for tooth movement?
- oxytalan fibers composed of fibrillin
82
What are the portion of fibrils anchored into mineralized cementum or bone?
- sharpeys fibers
83
What is the major ECM. component of dentin?
- collagen (mainly type I with trace amounts of type III and V)
- (90% of organic matrix)
84
What collagen is found at the DEJ?
- type IV
85
what collagen has been found at the DEJ that extends into enamel?
- type VII
86
What collagen might play a role in attachment of enamel to underlying dentin?
- type VII
87
Type ____ collagen is important in the basal lamina?
- Type IV
88
_____ underlies all epithelial cell layers and is synthesized by cells resting on it
- Basal lamina
89
What separates epithelium from underlying connective tissue stroma?
- Basal lamina
90
What is the function of the basal lamina in the kidney glomerulus?
- important in determining which molecules will pass into urine from blood (glomerular filtration) 🩸
91
What is the function of the basal lamina in the skin?
- critical for attaching epidermis (epithelial outer layer) to dermis
92
What is the function of basal lamina in the oral mucosa?
- critical for attaching epithelium to lamina propria
93
What are some of the other roles of basal lamina in addition to structural/filtration?
- determining cell polarity
- influencing cell metabolism
- regulating cell survival, proliferation, migration, differentiation
94
What are the key components of the basal lamina?
- glycoproteins
- collagens
- proteoglycans
95
What glycoproteins are in basal lamina?
- laminins (primary component/main organizer)
| - nidogen
96
What collagens are found in basal lamina?
- type IV collagen (provides tensile strength)
| - type VI collagen (at stromal interface)
97
What proteoglycans are in basal lamina?
- perlecan (proteoglycan)
98
Notes about type IV collagen
- 6 genes encode for it
- three different hetero trimers can be formed
- this complexity helps the basement membrane have different properties
99
Type _____ collagen is important in anchoring the epidermis to the underlying dermis
- VII
100
Type VII collagen forms ________ interacts with type I collagen in stroma and type IV collagen/laminin in basal lamina (together called basement membrane)
- anchoring fibrils
101
The basement membrane is?
- type VII collagen with basal lamina
102
What inherited disease is due to mutations in COL7A1?
- dystrophic epidermis bullosa
103
What collagen has an important function in anchoring epidermis to underlying dermis or epithelium to underlying stroma?
- Type VII
104
Dystrophic epidermis bullosa results in?
- very fragile skin/mucous membranes that blister easily and can be sloughed off, problems with lining of esophagus, etc.
105
What are the steps of collagen biosynthesis?
1. Synthesis of PRO- alpha chain
2. Hydroxylation of slected prolines and lysines
3. Glycosylation of selected hydroxylysines
4. Slef assembly of three pro alpha chains (C terminal ends bind together)
5. procollagen triple helix formation
6. secretion
7. Cleavage of proppeptides
8. self assembly into fibril
9. aggregation of collagen fibrils to form a collagen fiber
106
Why is collagen high in glycine?
- located at very 3rd residue and allows the collagen to pack tightly
107
In gly-X-y repeating motif the X is what and Y is?
- proline and
| - 4-hydroxyproline
108
Does collagen have a tertiary structure?
- nope
109
What makes up the quaternatery structure of collagen?
- three helical chains wind around each other to form a right handed triple helix
110
What stabilizes the triple helix of collagen?
- hydrogen bonding between amide hydrogen of glycine in one chain and carbonly oxygen residue x in an adjacent chain
- hydrogen bonding also occurs between OH groups and amide groups of residues in adjacent chains
111
What is the secondary structure of collagen alpha polypeptide chains?
- extended LEFT handed helix (collagen helix)
112
What stabilizes each collagen helix?
- static repulsion of pyrrolidone rings of proline and hydroxyproline residues
113
Proline confers ____ twist in molecule which disrupts other types of secondary structure from forming (e.g. alpha helices, beta sheets)
- 60 degree twist
114
Why does the glycine occupy every 3rd postion?
- least bulky side chain
| - allows three helical alpha chains to pack together to form a triple helix
115
Amino acids X and Y (proline, 4-hydroxyproline) are located where?
- outside so there is room for their bulkier side chains
116
Prolyl hydroxylases and lysyl hydroxylase
- hydroxylates selected prolines and lysines
| requires vitamin C as a cofactor
117
FKBP10
- accelerates protein folding
118
Collagen glycosyltranferases
- glycosylates selected hydroxylysines
119
Protein disulphid isomerase (PDI)
- catalyzes formation of interchain disulphide bonds between cysteines during nucleation of three polypeptide chains at C-terminus
120
Hsp47
Chaperone protein that binds to disulfied bonded collagen trimers and helps complete formation of triple helix
121
What are the C-propeptides important in procollagen processing?
- important in nucleation of 3 collagen chains to form collagen trimer
- but fibril formation only occurs after C and N pro peptides are removed to form tropocollagen
122
What is responsible for cleaving off N-propeptide?
- AdamsTS2
123
What is responsible for cleaving off C-propeptied?
- BMP-1/tolloid proteinases
124
What enzyme is important in collagen crosslinking?
- lysyl oxidases
125
What increases tissue fragility in collagen?
- inhibition of crosslinking
| - also reduces tensile strength of fibrils
126
What greatly increases the strength of collagen fibrils?
- covalent crosslinking between lysines of adjacent molecules
127
T/F amount of cross linking increases with aging
- T
