Download Collagen by Kati Feken - Illinois State University

Collagen
Crystal structure of
collagen which has
three identical helices
shown in blue, green,
and purple. Each helix
consists of 18 residues.
by Kati Feken
View down central
axis of same
collagen structure.
Sequence of each helix: XGPXGPXGPX GPRGQXGV with X=any amino
acid
*Structures made using Rasmol and pdb file 2WUH
Structure
• Composed of three
identical, left-handed
helices
• 3 amino acids per turn
• Sequence: Gly-X-Y
• Predominantly X=proline,
Y=proline or hydroxyproline
• Contains approximately 33%
glycine, 30%
proline/hydroxyproline, 37%
other peptides.
Importance of Glycine Residues
• Stacks along inside of
collagen molecule (shown
in red)
• Glycine residues are
important for maintaining
tight turns (3 residues per
turn).
• Provides flexibility of
structure
Sequence Alignment
-Portion of collagen molecules from a human, mouse, chicken, and dog.
-Shaded amino acids are conserved.
-Black=identical amino acids, Gray=similar amino acids, Blue=glycine, Pink=proline
Fibrils
Collagen molecules stack together to form fibrils. Above is an electron
micrograph of several fibrils. One molecule of collagen from these fibrils
are 3000Å in length and 15Å thick. The gaps formed between the
collagen molecules line up every 4 molecules, causing striations that are
640Å.
Structure Stability
• Intramolecular Crosslinks:
covalent bonds between
residues inside a collagen
molecule
• Intermolecular Crosslinks:
covalent bonds of residues
on different collagen
molecules
Structure Stability
• Crosslinks usually occur between lysine, hydroxylysine, and
histidine residues
Function
• Most abundant protein in humans and other vertebrates
(comprises about 25-35% of total protein in the body)
• Provides flexibility/stability & comprises most of bones,
connective tissues, tendons, ligaments, skin, etc
• Composes corneas
• Roles in cell adhesion and signaling
– E.g. Human discoidin domain receptors DDR1 and DDR2
are activated by collagen
• Can be used for cosmetic and burn surgery
• Denatures to form gelatin to use in food products,
pharmaceuticals, photography, and cosmetics.
Scurvy
• Occurs when vitamin C deficiency
• Vitamin C is a cofactor for enzymes prolyl and lysyl
hydroxylase which hydroxylate proline and lysine.
• Proline and lysine need to be hydroxylated for
crosslinking and hydrogen bonding (and therefore,
stabilizing collagen).
• Leads to weakened connective tissues and capillaries.
• Symptoms: bleeding of gums and bone/joint tissues,
bruising, hemorrhages, fatigue, yellowing skin.
Osteogenesis Imperfecta
•
•
•
•
Genetic disorder that causes fragile bones, low bone mass, and
problems with connective tissues (if person with disease survives at all)
Usually caused by mutation of two genes for collagen I
The changes in coding cause a different amino acid to be substituted
for a glycine residue
Depending on the amino acid substituted, can be mild or lethal.
Osteogenesis Imperfecta
Mild effect: Alanine
substituted for a glycine
•
• Moderately severe effect:
Cysteine, Serine, or Glutamic
Acid substituted for a glycine
• Lethal effect: Arginine,
Cysteine , Valine, Serine, or
Aspartic Acid substituted for a
glycine
*Pictures:Patient has cysteine in place of
a glycine residue.
References
Alberts, Bruce, Alexander Johnson, Julian Lewis, Martin Raff, and Keith Roberts. Molecular Biology of the Cell. 4th. London: Garland Science, 2007. Chapter 19. Print.
Branden, Carl, and John Tooze. Introduction to Protein Structure. 2nd. New York: 2010. <http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120150>.
Garland Publishing, 1999. 9-10. Print.
Can Fam Physician. 2008 October; 54(10): 1403–1406.
"Collagen alpha-1(XIX) chain precursor [Mus musculus]." NCBI. NCBI, 2010. Web. 5 Apr 2010.
<http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=protein&dopt=GenPept&RID=VMDYAF9E01N&log%24=prottop&blast_rank=10&list_uids=11432
6515>.
"COLLAGEN, TYPE I, ALPHA-1; COL1A1." Online Mendelian Inheritance in Men . John Hopkins University, 2010. Web. 16 March 2010.
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941>.
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<http://www.ncbi.nlm.nih.gov/protein/AAA36358.1?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum>.
Garrett, Reginald, and Charles Grisham. Biochemistry. 3rd. Belmont: Thomson Learning, Inc., 2005. 169-171. Print.
"Protein Alignment." msa.cgb.ki.se. Kalign, 2005. Web. 5 Apr 2010. <http://msa.sbc.su.se/cgi-bin/msa.cgi>.
Nelson, David, and Cox Michael. Lehninger Principles of Biochemistry. 5th. W.H. Freeman, 2008. Chapter 4. Print.
"Osteogenesis Imperfecta." The Collagen Molecule, Aggrecan, Hyaluronate and Osteogenesis Imperfecta. Web. 15 Mar 2010.
<http://cwcdaart.securesites.net/images_slides/images_slides_11.htm>.
Rauch, Frank, and Francis H. Glorieux. "Osteogenesis Imperfecta." Lancet. 363. (2004): 1377-1385. Print.
"Scurvy." Worth1000 Images. Web. 17 Mar 2010. <http://fx.worth1000.com/entries/214103/scurvy>.
Structure. 2009 Dec 9;17(12):1573-81.
Sweeney, Shawn M., Joseph P. Orgel, Andrzej Fertala, Jon D. McAuliffe, and Kevin R. Turner. "Candidate Cell and Matrix Interaction Domains on the Collagen Fibril,
the Predominant Protein of Vertebrates." Journal of Biological Chemistry. 283.30 (2008): 21187-21197. Print.