11/6: Collagen Structure and Function I Flashcards by Anita Maxwynn

Tissues not made up only of ________

Cells

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What is the extracellular space filled with?

Network of large macromolecules (extracellular matrix)

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What is composed from large reprtioire of proteins with various properties assembled into an organized network/meshwork, in close asociation with producer cells?

Extracellular matrix

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What are specialized tissues in which ECM is more abundant than cells?

Connective tissues

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What is the ECM critical in?

Many oral and craniofacial tissues:
Teeth/bone
Cartilage
Lamina propria beneath oral epithelium
Gingiva, periodontium

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What tissue is made of specialized mineralized CT?

Teeth/bone

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What tissue is made of proteoglycan-rich specialized CT?

Cartilage

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What tissue is composed of collagen fibers in a connective tissue or STROMAL matrix (similar to dermis of skin)

Lamina propria beneath oral epithelium

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What tissue is composed of a stromal matrix containing collagen?

Gingiva, periodontium

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What are the cells embedded in the matrix?

Stroma

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What are the major components of the stromal matrix?

Collagen embedded in polysaccharide ground substance of hyaluronan and proteoglycans/glyosaminoglycans

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What are stroma cells derived from?

Mesodermal lineage

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What do fibroblasts secrete?

ECM in most connective tissues

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In specialized tissues, what is ECM secreted by?

Other fibroblast-related cells (osteoblasts, chondrocytes, odontoblasts)

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What is a specialized matrix at interface between CT stroma and epithelium?

Basal lamina (separates them/anchors them)

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What is the basal lamina tethered to underlying CT by?

Type VII collagen anchoring dibrils (“basement mebrane” - refers to basal lamina combined with this layer of collagen fibrils)

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What is important in cell polarity?

Basal lamina

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What makes up the major proportion of the tissue?

Extracellular matrix

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What is the ECM traditionally viewed as?

Structurally stable material with function to provide support/anchorage to cells and tissues/damarcate boundaries between cells/tissues

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What is the function of the ECM in bone?

Support and locomotion
Calcium homeostasis
Skeleton protects brain, internal organs

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What is the function of the ECM in teeth?

Provides strength/structure to bone
Resists shear and compression forces associated with chewing

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What is the function of the ECM in cartilage?

Support and locomotion
Resilient - shock absorber for compressive forces associated with locomotion/mastication

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What is the function of the ECM in addition to structural roles?

Embryonic development (cell adhesion/migration/tissue morphogenesis)
Regulation of cell function (Signaling/growth/differentiation)
Tissue repair/wound healing
Angiogenesis

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What can the ECM be viewed as?

Composite material
(various building materials w/ different mechanical properties combined/organized to create a tissue with optimal mechanical properties)

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What are examples of diverse types of ECM?

Bone/teeth - calcified, hard ECM Cornea - optically transparent ECM Tendon - rope-like organization of collagen gives tensile strength in one direction

The ECM component of collagen provides what property?

Tensile strength

The ECM component of proteoglycans provide what property?

Resilience/resistance to compression

The ECM component of elastic provide what property?

Elasticity/resilience

The ECM component of fibrillin-1 (microfibrils) provides what property?

Controlled elasticity

The ECM component of mineral (hydroxyapatite) provides what property?

Strength, hardness, but also brittleness

Fibrous proteins are:

1. Structural (collagen, elastin, fibrillins - provide tensile strength, elasticity) 2. Adhesive (fibronectin, vitronectin, laminin - help cells attach to ECM)

What are long polysaccharides consisting of repeating dissaccharide units – often covalently linked to protein in the form of proteoglycans?

Glycosaminoglycans

What is the major structural component of ECM?

Collagens

What are 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 α-chains wound around each other in a rope-like superhelix

What do all collagen molecules contain?

At least one triple helical region (collagenous domain)

What is collagen divided into?

Fibrillar Non-fibrillar

What do fibrillar collagens assemble into?

Rod-like structures = collagen fibrils

What are the major fibrillar collagens?

I, II, III

What happens after fibrils form?

They are crosslinked between lysines of adjacent molecules

What is type I collagen?

Collagen found in tendon, bone, ligaments, dentin, skin

What is type II collagen?

Principle collagen in cartilage matrix

What chains encode type I collagen?

Heterotrimer of two alpha1 chains and one alpha2 chain

What genes encode type I collagen?

COL1A1 COL1A2

What do mutations in type I collagen genes associate with?

Osteogenesis imperfecta

How are collagen fibrils arranged?

3D arrays - parallel bundles - orthogonal lattices - concentric weaves - wickerwork pattern - fibrils in a swirling pattern

What are type II collagen chains?

homotrimer of alpha1 chains

What is type II collagen encoded by?

COL2A1

What do mutations in type II collagen cause?

Chondrodysplasias

What are examples of non-fibrillar collagen?

Type IV and VI Type VII

What type of collagen is an important role in basal lamina?

Type IV and VI

What type of collagen is a key component of anchoring fibrils that attach epithelia to underlying connective tissue?

Type VII

In collagenous domains, where is glycine present?

Every 3rd residue X is often proline and Y is 4-hydroxyproline

How does each collagen helix get stabilized?

By static repulsion of pyrrolidone rings of proline and hydroxyproline residues

How do right handed triple helixes occur?

Three helical alpha-chains wind around each other

For each Gly-X-Y, what forms between the amide hydrogen of a glycine in one chain and carbonyl oxygen of residue X in adjacent chain?

Hydrogen bond

Where does hydrogen bonding occur?

Between OH groups and amide groups of residues in adjacent chains

What position does glycine occupy?

3rd position - least bulky side chain, lets three alpha helix chains pack together to form a triple helix

What are pos translational modifications of collagen important in?

Biosynthesis and assembly

What does collagen undergo prior to triple helix formation?

Extensive post translational modifications

What assist in correct trimerization and folding?

Several enzymes/molecular chaperones

What do prolyl hydroxylases and lysyl hodroxylases do?

Hydroxylates prolines and lysines - requires vitamin C as cofactor

What does FKBP10 do?

Accelerates protein folding

What does collagen glycosyltransferase do?

Glycosylates selected hydroxylysines

What does protein disulphide isomerase (PDI) do?

Catalyzes formation of interchain disulphide bonds between cysteins during nucleation of 3 polypeptide chains at c-terminus

What does Hsp47 do?

Binds to disulfide bonded collagen trimers and helps complete formation of the triple helix

What is important for fibril formation?

Proteolytic processing of procollagen molecules

What is important in nucleation of three collagen chains to form a collagen trimer?

C-propeptides

When does fibril formation only occur?

After C and N propeptides are removed to form tropocollagen

What do BMP-1/tolloid proteinaes do?

Cleave off c-propeptide

What do ADAMTS2,3,14 do?

Cleave off n-propeptide

What stabilizes the collagen fibrils?

Collagen crosslinking

What are key enzymes in crosslinking?

Lysyl oxidases

What occurs with inhibition of crosslinking?

Reduced tensile strength of fibrils/increases tissue dragility

When does the amount of crosslinking increase?

With aging

What is the only calcified tissue that doesn't contain abundant collagen?

Enamel

What attaches cementum layer of tooth root to alveolar bone?

Collagen in periodontal ligament

What contains abundant collagen fibers to attach gingiva to tooth and alveolar bone?

Gingiva

What are functions of collagen fibers in the gingiva?

− Anchoring gingival tissue to tooth/ alveolar bone − Resisting masticatory forces

What are the five groups that collagen fibers are classified into?

Dentinogingival Alveogingival Circumferential Periosteal Transseptal

What is calcified into cementum/bone at one end, free at other end?

Dentinogingival/alveogingival

What is the function of dentinogingival/alveogingival fiber?

Hold free gingiva against tooth

What fiber encirlces the tooth?

Circumferential

What fiber holds attached gingiva against bone?

Periosteal

What fiber runs between teeth?

Transseptal

What collagen makes up the periodontal ligament?

Type I collagen

What fibers are contained inside periodontal ligament?

Oxytalan fibers composed of fibrillin

What are portions of fibrils anchored into mineralized cementum or bone?

Sharpey's fibers

What collagen restricted to narrow zone at the DEJ?

Type IV

What collagen found in enamel organic matrix adjacent to DEJ?

Type VII - fibers surround enamel rods

What fiber may play a role in attachment of enamel to underlying dentin?

Type VII

What collagen is important in basal lamina?

Type IV

What is the basal lamina important for in kidney glomerulus?

determining which molecules will pass into urine from blood (glomerular filtration)

What is the basal lamina important for in skin?

Attaching epidermis (epithelial outer layer) to dermis

What is the basal lamina important for in oral mucosa?

Attaching epithelium to lamina propria

What are other roles in addition to structural/filtration?

- Determining cell polarity - Influencing cell metabolism - Regulating cell survival, proliferation, migration, differentiation

What are key components of the basal lamina?

Glycoproteins Collagens Proteoglyvans

What are glycoproteins in the basal lamina?

Laminins (primary component/main organizer) Nidogen

What collagen provides tensile strength in the basal lamina?

Type IV collagen

What are proteogylcans in the basal lamina?

Perlecan (proteoglycan)

What genes encode type 4 collagen alpha chains?

COL4A1 COL4A2 COL4A3 COL4A4 COL4A5 COL4A6

What 3 heterotrimers can be formed in the basal lamina?

alpha 1,1,2 alpha 3,4,5 alpha 5,5,6

What forms anchoring fibrils?

Type VII collagen

What interacts with type I collagen in stroma and type IV collagen/laminin in basal lamina?

Anchoring fibrils

What does type VII collagen anchor?

epidermis to underlying dermis or epithelium to underlying stroma

What occurs due to a mutation in COL7A1?

Dystrophic epidermis bullosa

What results in very fragile skin/mucous membranes that blister easily and can be sloughed off, problems with lining of the oesophagus?

Dystrophic epidermis bullosa