Collagen Structure and Function Part 1 Flashcards
non-cellular component of tissues (outside the cells) that provides support and structure to the tissue. Made up of many fibrous proteins, etc.
Extracellular Matrix (ECM)
proteins secreted outside the cell that compose the extracellular matrix
Extracellular Matrix Protein
the supportive framework of a tissue composed of connective tissue (cells + extracellular matrix)
Connective Tissue Stroma
layer of extracellular matrix that separates epithelial cells from (but keeps them adhered to) the underlying stroma
Basal Lamina
long unbranched polysaccharides consisting of a repeating disaccharide unit
Glycosaminoglycan (GAG)
a protein that is highly glycosylated (consists of a core protein that is covalently attached to GAG side chains)
Proteoglycan
a protein with covalently attached oligosaccharides (sugar chains)
Glycoprotein
a bond that links one protein chain to another
Crosslinking
a protein made up of three identical polypeptide chains
Homotrimeric
a protein made up of three non-identical polypeptide chains
Heterotrimeric
the mature collagen molecule (after post translational modifications, assembly into a trimer and cleavage of the N and C propeptides) – this is the basic building block of collagen fibrils
Tropocollagen
a fancy word for a very large molecule!!
Macromolecule
a fancy word for a polymeric structure containing a large number of molecules linked together
Supramolecular
composed from large repertoire of specialized ECM proteins with various properties assembled into an organized network/meshwork, often in close association with producer cells
ECM
specialized tissues in which ECM is more abundant than cells.
Connective tissues
specialized mineralized connective tissues of the skeletal system
Teeth/Bone
proteoglycan-rich specialized connective tissue
Cartilage
______ is beneath oral epithelium – composed of collagen fibers in a connective tissue or STROMAL matrix
Lamina Propria
have a stromal matrix containing collagen
Gingiva, periodontium
cells embedded in matrix
STROMA
collagen embedded in polysaccharide ground substance of hyaluronan+ proteoglycans/glyosaminoglycans compose
stromal matrix
STROMAL CELLS –derived from _____ lineage
mesodermal
_____ secrete ECM in most connective tissues
Fibroblasts
Specialized matrix at interface between connective tissue stroma and epithelium (separates them); important in polarity
Basal lamina
Basal lamina is tethered to underlying connective tissue by _______ anchoring fibrils
type VII collagen
–refers to the basal lamina combined with this layer of collagen fibrils
Basement membrane”
Traditionally viewed as structurally stable material whose function is to provide support/anchorage to cells and tissues/demarcate boundaries between cells/tissues
ECM
ECM functions in Support and locomotion-Calcium homeostasis-Protects brain, internal organs in ___
bone
ECM functions in Provides strength/structure - Resists shear and compression forces associated with chewing _____
teeth
ECM functions in Support and locomotion- Resilient - shock absorber for compressive forces associated with locomotion, mastication etc. in
cartilage
_____ plays roles in Embryonic Development (cell adhesion / migration / tissue morphogenesis)-Regulation of Cell Function (signaling / growth / differentiation)-Tissue Repair/wound healing-Angiogenesis
ECM
___ functions in ECM to provide tensile strength
collagen
____ funciton in ECM in resilience/ resistance to compression
Proteoglycans
_____ function in ECM in elasticity and resilience
Elastin
_____ function in ECM in controlled elasticity
Fibrillin-1
_____ function in ECM in strength, hardness, and brittleness
Mineral
Long polysaccharides consisting of repeating dissaccharide 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
Major structural component of ECM; Trimeric molecules consisting of three identical (homotrimeric) or non-identical heterotrimeric polypeptide chains-α-chains; divided into fibrillar and non-fibrillar
collagen
Which collagens make up the fibrillar collagens?
I, II, III, V, XI
____ assemble into higher order rod-like structures (collagen fibrils)
fibrillar collagens
Which collagens are the main fibrillar collagens?
I, II, and III
After fibrils form they are _____ between lysines of adjacent molecules which greatly increases tensile strength
crosslinked
principle collagen found in tendon, bone, ligaments, dentin, and skin (occurs in ECM as elongated fibrils)
Type I collagen
Principle collagen in cartilage matrix
Type II collagen
Collagen that is important in dermal reticular fibers
Type III collagen
Collagen that is associated with type I that may regulate the assembly of heterotypic fibers
Type V collagen
Collagen found in cartilage and eye; helps regulate spacing/ diameter of type III collagen fibrils
Type XI collagen
What genes code for collagen chains?
COLIA1 and COLIA2
T/F: Type 1 Collagen is a heterotrimer
True
Mutations in the type I collagen genes leads to
osteogenesis imperfecta
The heterotrimer of type I collagen is made up of ___ alpha chains and ____ beta chains
2 alpha and 1 beta
T/F: Type 2 collagen is a homotrimer
True
Type 2 collagen consists of __ alpha chains and ___ beta chains
3 alpha and 0 beta
Mutations in type 2 collagen causes
chondroplasias
____ collagens contain Triple helical domains shorter, interrupted by non-collagenous sequences- structureless rigid,more flexible
non-fibrillar
Type IV, VI-X, XII-XXIII, XXV, XXVI, XXVIII are ___ collagens
non-fibrillar
Type ___ and ____ collagen have an important role in basement membrane
IV and VI
Type ___ collagen are a key component of anchoring fibrils that attach epithelia to underlying connective tissue
VII
Type ___ collagen is a major ECM component of dentin, cementum, and periodontal ligament
I
___ only calcified tissue that does not contain abundant collagen
Enamel
____ function in gingiva to anchor tissue to tooth/ bone and resist masticatory forces
collagen
Collagen in gingiva that are calcified into cementum/ bone at one end and are free at the other end; hold free gingiva against tooth
dentinogingival/ alveogingival collagen
Collagen in gingiva that encircle the tooth
circumferential collagen
Collagen in gingiva that hold attached gingiva against bone
periosteal collagen
Collagen in gingiva that run between teeth
Transseptal collagen
____ is composed of mainly type 1 collagen and contains oxytalan fibers composed of fibrillin,
periodontal ligament
portion of fibrils anchored into mineralized cementum or bone
Sharpey’s fibers
Type ___ collagen is restricted to narrow zone at DEJ
IV
Type ___ collagen is found in enamel organic matrix adjacent to DEJ; fibers surround enamel rods; may play role in attachment of enamel to underlying dentin
VII
____ underlies all epithelial cell layers (synthesized by cell resting on it); separates epithelium from underlying CT stroma; determines cell polarity, influences cell metabolism, and regulates cell survival, proliferation, migration, and differentiation
Basal lamina
In Kidney glomerulus ________: important in determining which molecules will pass into urine from blood
basal lamina
In skin _______: critical for attaching epithelium to lamina propria
basal lamina
What are the 3 key components of basal lamina?
glycoproteins, collagens, and proteoglycans
What is the primary component/ main organizer of basal lamina?
laminins
_______ collagen forms anchoring fibrils that interact with type 1 collagen in stroma and type IV collagen / laminin in basal lamina (BM); important function in anchoring epidermis to dermis or epithelium to underlying stroma
type VII collagen
Inherited disease due to mutations in COL7A1 that results in very fragile skin/ mucous membranes that blister easily and can by sloughed off, problems with lining of esophagus
dystrophic epidermis bullosa
Steps of Collagen synthesis
Synthesis of pro chain => Hydroxylation of selected prolines and lysines => glycosylation of selected hydroxylysines => self-assembly of 3 pro alpha chains => procollagen triple helix formation (nucleation at C-propeptide) => secretion => cleavage of propeptides => self-assembly into fibril => aggregation of collagen fibrils to form a collagen fiber
Primary structure of collagen is primarily made up of what amino acid?
Glycine
Secondary structure of collagen alpha polypeptide chains (left handed) called
collagen helix
_____ (aa) confers a 60 degree twist in molecule which disrupts other types of secondary structure
proline
each ____ is stabilized by static repulsion of pyrrolidone rings of proline and hydroxyproline residues
collagen helix
3 helical alpha chains wind around each other to form a right handed ____
triple helix
____ stabilizes triple helix of collagen
hydrogen bonding
_____ occupies every 3rd residue of collagen because it is the least bulky side chain
glycine
T/F: Collagens undergo extensive post translational mods in ER prior to triple helix formation
True
T/F: Several enzymes/ molecular chaperones assist in correct dimerization and folding
False; trimerization
T/F: Post translational mods of collagen is a coordinated process that must happen at the proper time
True
Strength of collagen fibrils greatly increased by covalent crosslinking between _____ of adjacent molecules
lysine
