Thursday, March 20, 2014

Biochemistry: Connective Tissue Proteins (Collagen)

To read the complete version access from the following link:
https://drive.google.com/file/d/0B52shws9yAJZRnMtWlNVVEN0aDA/edit?usp=sharing



An excerpt of the lecture note:

 Connective Tissue Proteins
70-80% of our body structures are made of connective tissue proteins: skin, bone, cartilage, ligament, tendon, ground substance

3D structure: (globular vs fibrous)
1)    Globular protein:
a.   Water soluble
b.   Hemoprotein, plasma (in blood, because it’s soluble), membrane protein
c.    Complex
d.   Biochemical and Biophysical role

2)    Fibrous protein (helps form the Connective Tissues):
a.   Water insoluble
b.   Simple structure
c.    Structural and mechanical (bone, cartilage, ligament, etc.)
d.   Large amount in our body

Collagen (most important): 교원성 단백질
a.   Major protein that forms CT of multicellular organisms
b.   High tensible strength
c.    Water-insoluble
d.   Made from at least 11 types of genes
e.   Various post-translational modification, depending on the mechanical role (where they are located in the organism).
f.     Type I-V usually studied in labs

I. Structure:
Insoluble in water, so we need to find a collagen version that is soluble to study it. Collagen’s precursor is water soluble!: Tropocollagen.

Tropocollagen:
1.    3 polypeptide chain: 3 chains coiled together to make a triple standard helical rod (fiber). 15A height. Helical fold (between each length is a helix). 1 molecule has 3000A length. So around 1000 helix. Triple helix so, 3000 a.a..  α1 and α2 are 95kDa each. Average a.a. MW is 120kDa, so 95kDa is quite low. 

2.    Unusual amino acid composition and sequence:
1.    Every 3rd a.a. is a glycine: explains why collagen’s a.a. has 95kDa (much lower than the average a.a. MW 120kDa).
2.    4-OH-Pro and 5-OH-lys hydroxylation exists in 9% of the structure.
3.    Repeated sequence: X-Y-Gly-Pro-(4-OH-Pro)-Gly. (only couple others like elastin and silk have a repeated sequence)
3. Hydroxylation of proline and lysine residues of nascent chain (this means that hydroxylation occurs on precursors that were immediately made from the DNA, fresh!):

Summary:
DNA (transcription + translation) à nascent chain (post-translational modification) à procollagen à tropocollagen à collagen


III. Tropocollagen’s synthesis and maturation:


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