In this chapter you will learn: Structure of myoglobin and hemoglobin similar; understand oxygen binding curves (where high and low affinity binding occurs); understand positive cooperatively in relationship to oxygen binding to hemoglobin, be able to describe this in relationship to protein conformation and the sigmoidal oxygen binding curve; be able to describe T and R conformations of Hb; understand how oxygen binding changes Hb conformation; define allosteric interaction;. | Chapter 4 (part 3) 3-D Structure / Function Animal Scrapie: sheep TME (transmissible mink encephalopathy): mink CWD (chronic wasting disease): muledeer, elk BSE (bovine spongiform encephalopathy): cows Human CJD: Creutzfeld-Jacob Disease FFI: Fatal familial Insomnia Kuru PrPC PrPSc solubility soluble non soluble structure predominantly alpha-helical predominantly beta-sheeted multimerisation state monomeric multimeric (aggregates) infectivity non infectious infectious Susan W. Liebman, and James A. Mastrianni (2005) Trends in Molecular Medicine 11: 439-441 Myoglobin/ Hemoglobin First protein structures determined Oxygen carriers Hemoglobin transport O2 from lungs to tissues Myoglobin O2 storage protein Mb and Hb subunits structurally similar 8 alpha-helices Contain heme group Mb monomeric protein Hb heterotetramer (a2b2) myoglobin hemoglobin Heme group Heme = Fe++ bound to tertapyrrole ring (protoporphyrin IX complex) Heme non-covalently bound to globin proteins through His residue | Chapter 4 (part 3) 3-D Structure / Function Animal Scrapie: sheep TME (transmissible mink encephalopathy): mink CWD (chronic wasting disease): muledeer, elk BSE (bovine spongiform encephalopathy): cows Human CJD: Creutzfeld-Jacob Disease FFI: Fatal familial Insomnia Kuru PrPC PrPSc solubility soluble non soluble structure predominantly alpha-helical predominantly beta-sheeted multimerisation state monomeric multimeric (aggregates) infectivity non infectious infectious Susan W. Liebman, and James A. Mastrianni (2005) Trends in Molecular Medicine 11: 439-441 Myoglobin/ Hemoglobin First protein structures determined Oxygen carriers Hemoglobin transport O2 from lungs to tissues Myoglobin O2 storage protein Mb and Hb subunits structurally similar 8 alpha-helices Contain heme group Mb monomeric protein Hb heterotetramer (a2b2) myoglobin hemoglobin Heme group Heme = Fe++ bound to tertapyrrole ring (protoporphyrin IX complex) Heme non-covalently bound to globin proteins through His residue O2 binds non-covalently to heme Fe++, stabilized through H-bonding with another His residue Heme group in hydrophobic crevice of globin protein Oxygen Binding Curves Mb has hyberbolic O2 binding curve Mb binds O2 tightly. Releases at very low pO2 Hb has sigmoidal O2 binding curve Hb high affinity for O2 at high pO2 (lungs) Hb low affinity for O2 at low pO2 (tissues) Oxygen Binding Curve Oxygen Binding Curve O2 Binding to Hb shows positive cooperativity Hb binds four O2 molecules O2 affinity increases as each O2 molecule binds Increased affinity due to conformation change Deoxygenated form = T (tense) form = low affinity Oxygenated form = R (relaxed) form = high affinity O2 Binding to Hb shows positive cooperativity O2 Binding induces conformation change T-conformation R-conformation Heme moves nm Exposing crystal of deoxy-form to air cause crystal to crack Show Movie Allosteric Interactions Allosteric interaction occur when specific molecules bind a protein and modulates activity
