Class Notes (809,484)
Canada (493,749)
BIOC12H3 (56)

BIOC12Fall2012 Lecture Week 7 Notes

9 Pages
Unlock Document

University of Toronto Scarborough
Biological Sciences
Rongmin Zhao

BIOC12FALL2012 Lecture Week 7: Protein Functions (Chapter 15) Myoglobin  Small intracellular protein in vertebrate muscles  only in cardiac myocytes and skeletal muscle fibres  The colour of myoglobin usually represents the colour of meat (red or purple)  Immunohistochemical localization of myoglobin in differentiated mouse C2C12 Myotubes  green= myoglobin, red= nucleus   whale sperm myoglobin  contains 153 amino acids (sperm whale myoglobin)  first protein wih known x-ray structure  human myoglobin contains 154 amino acids  contains 8 helices: A-F and short inter helices region such as CD, EF and GH   myoglobin can bind O 2  the major function of myoglobin is to facilitate oxygen diffusion in muscles  acts as oxygen storage  myoglobin is not essential for muscles under normal conditions (knockout mice are normal) Myogloin contains a Heme group  heme is a porphyrin derivative conaining 4 pyrrole groups (proline side cian is a pyrrolidine group)  heme occurs in many proteins: myoglobulins, hemoglobulin, neuroglobulin, cytochrome c etc  heme sits in a hydrophobic pocket  oxygenation alters the electronic state of the Fe2+-Heme complex and causes the colour change  Fe2+ is coordinated by His F8  ferrous ions interacts with six ligands Mb  4 of these are the N atoms of the porphyrin 1  a 5 ligand is donated by the imidazole side chain of amino acid residue His F8  this residue is on the 6 th th or F helix and it is the 8 residue in the helix, hence its name  when myoglobin binds oxygen, then O2 molecule adds to the heme iron as the sixth ligand  the O2 molecule is tilted relative to a perpendicular to the heme plane   the heme is tightly held in the myoglobin molecule  Val E11 and Phe CD1 help to hold the heme in place O 2inding Alters Mb Conformation  In deoxymyoglobin, the ferrous ion actually lies o.55A above the plane of the heme  When oxygen binds to Fe in heme of Mb, the heme Fe is drawn toward the plane of the porphyrn ring  With oxygen bound, the Fe2+ atom is only 0.26A above the plane  For Mb, this small change has little consequence Oxygen binding property Mb+O 2MbO 2 Dissociation constant: [Mb][O2] [Mb][O 2 k = Þ[MbO ]2 (1) [MbO 2 k The dissociation constant is often ed ressed as k Fractional saturation: defined as the fr2ction of O -binding site occupied by O2 [MbO ] YO2 = 2 (2) [Mb]+[MbO ] 2 Substitute [2bO ] in (2) by the formula (1): [O ] Y = 2 O2 k +[O ] 2   since O2 is a gas, [O2] is usually expressed as the partial pressure (oxygen tension), pO2  Therefore: Oxygen Binding Curve of Myoglobin 2   this function is a rectangular hyperbola  k is the value of pO2 at 50% MbO2 saturation  1 atm = 760 torr = 760 mmHg Hemoglobin  hemoglobin is a tetramer   hemoglobin alpha and beta and human myoglobin share very high similarity of amino acids  hemoglobin is located in red blood cells  structurally (homologue) related to myoglobin  but only 18% of residues are identical in myoglobin and in the alpha and beta subuntis of hemoglobin  functions for O2 transport  Hb has an α β tetrameric structure 2 2  Figure above: an ab dimer of Hb, with packing contacts indicated in blue  the sliding contacts made with the other dimer are shown in yellow  Hemoglobin is in an exact C2 symmetry structure  protomer αβ  Hemoglobin is in a pseudo-D2 symmetry  becase the alpha and beta subunits are not exactly the same  Hemoglobin binds O2 showing a sigmoidal binding curve   sigmoidal curve – S shaped  comparing the hyperbola curve: at low pO2, lower binding and at high pO2, higher binding for sigmoidal mode  sigmoidal binding curve always shows a cooperative binding  binding of one ligand affects the other ligand binding sites  hyperbola binding curve always shows an independent binding  binding of one ligand does not affect the other ligand binding sites An Alternative O2-Binding curver for Hb 3  oxygen saturation curve for Hb in the form of Y vs. pO2 assuming n=4 and P50 =26 torr  Y is the fractional saturation of Hb    a comparison of the experimentally observed O2 curve (blue) for Hb yielding a value for n of 2.8, the hypothetical curve if n=4 in pink, and the curve if n=1 (non interacting O2- binding sites) in grey  The Conformation Change  the secret of Mb and Hb  oxygen binding changes the Mb conformation  without oxygen
More Less

Related notes for BIOC12H3

Log In


Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.