Understanding>> | |||||||||||||||||||||
Basics of Sickle Cell | Who suffers from it? | What is Hemoglobin? | Fiber formation | Protein | |||||||||||||||||
In sickle cell hemoglobin, fiber formation occurs when individual hemoglobin molecules stick together. This process happens in sickle cell hemoglobin because of the genetic mutation that leads to a change in a single amino acid residue of the protein sequence. In sickle cell hemoglobin the changed or mutated amino acid is hydrophobic. The literal meaning of hydrophobic is 'fear of water.' This is not exactly the case in hemoglobin. This amino acid change occurs on the surface of the sickle cell hemoglobin Since the cellular environment of red blood cells is similar to water, the amino acid change causes the hemoglobin to associate with other hemoglobin molecules rather than with the cellular environment. This preferential interaction of the hemoglobin molecules with each other rather than water is attributed to a 'hydrophobic interaction' of certain amino acid residues, one of which is the mutated residue, b6 Valine.
Going deeper: hydrophobic interactions of amino acids
Fiber formation occurs through two main stages, referred to as the double nucleation mechanism (Fig 4.6). In the first stage individual hemoglobin molecules have to come together to form a nucleus, that will be the initiation point for the fibers. Approximately, seven hemoglobin molecules need to come together to form this nucleus. This process is relatively slow, because of the number of molecules that need to come together to form the nucleus. Once the nucleus is formed the second stage of the process begins. In this second stage, fiber formation is relatively rapid because fibers can build on the pre-existing structure. Practically, this means that it is not necessary to bring so many molecules together at once, which significantly speeds up the process.
Our
laboratory is interested in understanding the mechanics of the first or
initial stage of the fiber formation process.
If this process can be extended to match that of the circulation
time in the body, then the Red Blood Cells (RBCs) would become exposed to oxygen before a
significant amount of fibers could form.
We believe that this would be extremely beneficial in the treatment
of sickle cell disease. (link to the research pages) |
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