It is well known that haemoglobin is essential for transport
of oxygen around the body, and its structure is key for its correct
functionality. However, it also
exhibits a less well known, detrimental behaviour. During tissue damage and
haemolysis (rupturing of red blood cells), haemoglobin is released into plasma
where it will dissociate into αβ dimers1.
This can potentially be harmful to cells, as haem is highly reactive and is
able to participate in chemical reactions as well as generate free radicals1.
This problem is overcome through the instant capture of αβ dimers by
haptoglobin1.
This is one of more than 30 different acute phase proteins which will be
released as a result of damaged tissue2.
Haptoglobin binds these haemoglobin dimers, forming a complex and protecting
tissues from oxidative damage1.
Furthermore, the complex is recognised and bound by the macrophage scavenger
receptor CD163: an acute phase-regulated transmembrane protein, which will
engulf haemoglobin dimers to mediate rapid clearance3.
Finally, the complex prevents renal filtration of haemoglobin and therefore in
turn prevents toxicity in the kidneys1.
Anderson et al. chose to use porcine blood in order to
investigate the structure of this complex because previous studies using human
blood have proven unsuccessful. The porcine haptoglobin-haemoglobin complex has
82% sequence identity with the complex in humans, meaning they will have very
similar structures and therefore the results will be relevant to the human
equivalent. The overall structure, as seen below, has two-fold rotational
symmetry and resembles a barbell, with the molecular dimensions of 180 Å x 65 Å x 50 Å.They were able to
successfully determine the structure to a resolution of 2.9 Å.
Fig. 1 Animation of the porcine haptoglobin-haemoglobin structure. Haptoglobin
is shown in blue and cyan, haemoglobin dimers in red and pink.
The introduction is brief and well organised, I can understand the content easily. The movie of the protein complex is nice. It gives a whole view of how the complex looks like.
ReplyDeleteI agree, very clear and engaging introduction. I love the background, very attractive but not too distracting.
ReplyDeleteThe information was organised quite well and was easy to understand thanks to the pymol images. The biological relevance section was a good way to highlight the importance of the complex.
ReplyDeleteGood use of the video. The introduction was informative and to the point. The template choice is also very subtle and adds to the easy read of the blog.
ReplyDeleteHey - really liked your site. I found the layout clear and easy to navigate (I especially enjoyed the background, clever!). The language was easy to read, and your PyMol pictures were detailed and clearly labelled. I also liked figure 6 - it provided a good break-down of the interactions.
ReplyDeleteOverall I liked the site very much. The introduction was concise and easy to understand. The organization of the pages were also very easy to follow and each page contained just enough detail to be informative but is still to the point. The pymol pictures are clear and compliment the informative text excellently. I liked the background image as well as it suits the theme and subject of the discussion perfectly.
ReplyDeleteGreat job. Your site is very well organised, making it easy to follow and understand the findings of the paper. The animation of the complex and the pymol pictures are very helpful.
ReplyDeleteVery well organized and info is well explained. Good use of video and pymol images
ReplyDelete