Figure 1. Hb-Hp/CD-163 Pathway during Intravascular hemolysis by Ololade Fatunmbi </b>]]
Haptoglobin-Hemoglobin Structure
Hemoglobin (Hb) is arguably one of the most studied proteins of all time. Hb is essential for life because it transports oxygen from organs to tissues so that we can have energy. Like most entities in life, too much of something may actually harm you. High concentrations of Hb released from red blood cells could cost oxidative damage to the body. In order to prevent this, haptoglobin 1-1 (Hp), an abundant glycoprotein in blood binds free hemoglobin (Hb) dimers in one of the strongest non-covalent binding events known in biology and
Function
During intravascular hemolysis Hb which is physiological a is released from red blood cells in to the extracellular environment. When Hb is in the extracellular environment, then dissociates into dimers exposing and could react with .
Hp binds shields Hb and shields these redox active residues and exposes and epiptope recognized by the multifunctional receptor, CD163.
Structural highlights
Hp' structure
Hp alone's crystal structure has not yet been elucidated. Hp1-1 is ~90kda and consists of dimer of the α1 (light) and β (heavy) chain linked by disulfide bond (Cys33). There are altogether 4 disulfides bonds (cys72 and cys 105) hold the light and heavy chain together). There are also 4 n-linked glycosylation sites found on a monomer of Hp1-1 (16).
Hb-Hp's Complex Structure
What makes the binding between Hp so tight and nearly irreversible? The interaction between Hb and Hp is composed of various hydrophobic and electrostatic interactions.
Disease
This process accounts for approximately 15% of total red blood cell destruction and occurs in several diseases including sickle-cell anemia and malaria (1).
Antibacterial Activity
When hemoglobin becomes non-covalently bound to haptoglobin, Hb and iron are no longer available to Escherichia coli and other bacteria that require iron (7). Eaton was able to demonstrate that when Hp was given to rats that have been intraperitoneally injected with E. Coli and hemoglobin, Hp was able to prevent fatal effects (8).
Antioxidant Activity
Haptoglobin has a significant role as an antioxidant (9). Free hemoglobin also increases the peroxidation of purified arachidonic acid and other polyunsaturated fatty acids within neuronal cell membranes (10). Iron released from heme proteins can catalyze oxidative injury to neuronal cell membranes and might have a role in posttraumatic central nervous system (CNS) damage (10). Haptoglobin, binds to Hb and removes it from the circulation and prevents iron-stimulated formation of oxygen radicals (11).
Prevention of Renal Damage
Another consequence caused by free hemoglobin is oxidative damage in renal tissues following intravascular hemolysis (7). Yet when haptoglobin binds to hemoglobin, the complex is too large to pass through the glomeruli of the kidney and will be removed via the reticuloendothelial system (7). Therefore Hb induced injury to the parenchyma is prevented by haptoglobin (12).
Relevance
(http://www.umass.edu)
My Research Interest
I am focused on structural elucidation of Hp and it's interact physiological partners through molecular modeling and native mass spectrometry.
This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
</StructureSection>
References
Ololade Fatunmbi. Click above on edit this page to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.
