Presentation on theme: "Collagen by Kati Feken Crystal structure of collagen which has three identical helices shown in blue, green, and purple. Each helix consists of 18 residues."— Presentation transcript:
1Collagen by Kati FekenCrystal structure of collagen which has three identical helices shown in blue, green, and purple. Each helix consists of 18 residues.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
2Structure Composed of three identical, left-handed helices 3 amino acids per turnSequence: Gly-X-YPredominantly X=proline, Y=proline or hydroxyprolineContains approximately 33% glycine, 30% proline/hydroxyproline, 37% other peptides.
3Importance 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
4Sequence 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
5FibrilsCollagen 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.
6Structure StabilityIntramolecular Crosslinks: covalent bonds between residues inside a collagen moleculeIntermolecular Crosslinks: covalent bonds of residues on different collagen molecules
7Structure StabilityCrosslinks usually occur between lysine, hydroxylysine, and histidine residues
8FunctionMost 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, etcComposes corneasRoles in cell adhesion and signalingE.g. Human discoidin domain receptors DDR1 and DDR2 are activated by collagenCan be used for cosmetic and burn surgeryDenatures to form gelatin to use in food products, pharmaceuticals, photography, and cosmetics.
9Scurvy 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.
10Osteogenesis 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 IThe changes in coding cause a different amino acid to be substituted for a glycine residueDepending on the amino acid substituted, can be mild or lethal.
11Osteogenesis Imperfecta Mild effect: Alanine substituted for a glycineModerately severe effect: Cysteine, Serine, or Glutamic Acid substituted for a glycineLethal effect: Arginine, Cysteine , Valine, Serine, or Aspartic Acid substituted for a glycine*Pictures:Patient has cysteine in place of a glycine residue.
12ReferencesAlberts, Bruce, Alexander Johnson, Julian Lewis, Martin Raff, and Keith Roberts. Molecular Biology of the Cell. 4th. London: Garland Science, Chapter 19. Print. Branden, Carl, and John Tooze. Introduction to Protein Structure. 2nd. New York: <http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120150>. Garland Publishing, Print. Can Fam Physician October; 54(10): 1403–1406. "Collagen alpha-1(XIX) chain precursor [Mus musculus]." NCBI. NCBI, Web. 5 Apr <http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=protein&dopt=GenPept&RID=VMDYAF9E01N&log%24=prottop&blast_rank=10&list_uids= >. "COLLAGEN, TYPE I, ALPHA-1; COL1A1." Online Mendelian Inheritance in Men . John Hopkins University, Web. 16 March "Collagen type XI alpha 2 [Canis familiaris]." NCBI. NCBI, Web. 5 Apr <http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=protein&dopt=GenPept&RID=VMDYAF9E01N&log%24=prottop&blast_rank=71&list_uids= >. "Collagen, type XXII, alpha 1 [Gallus gallus]." NCBI. NCBI, Web. 5 Apr 2010 <http://www.ncbi.nlm.nih.gov/protein/NP_ ?log$=ACCN>. "Collagen [Homo sapiens]." NCBI. NCBI, Web. 5 Apr <http://www.ncbi.nlm.nih.gov/protein/AAA ?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum>. Garrett, Reginald, and Charles Grisham. Biochemistry. 3rd. Belmont: Thomson Learning, Inc., Print. "Protein Alignment." msa.cgb.ki.se. Kalign, Web. 5 Apr <http://msa.sbc.su.se/cgi-bin/msa.cgi>. Nelson, David, and Cox Michael. Lehninger Principles of Biochemistry. 5th. W.H. Freeman, Chapter 4. Print. "Osteogenesis Imperfecta." The Collagen Molecule, Aggrecan, Hyaluronate and Osteogenesis Imperfecta. Web. 15 Mar <http://cwcdaart.securesites.net/images_slides/images_slides_11.htm>. Rauch, Frank, and Francis H. Glorieux. "Osteogenesis Imperfecta." Lancet (2004): Print. "Scurvy." Worth1000 Images. Web. 17 Mar <http://fx.worth1000.com/entries/214103/scurvy>. Structure Dec 9;17(12): 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 (2008): Print.