Sculpting molecules guide body cell curves
5 June
Knowing the exact architecture of a minute structure found deep within body cells may not have an immediately obvious application, but when you consider how a healthy body relies not only on harmonious function of whole organs but on the hectic array of messages and frenzy of activity that buzz between individual cells, the importance of that tiny structure is magnified.
Knowledge of the structures that build body cells, how they fit and work together can provide unexpected clues in the challenge of learning what causes disease, how genetic variety influences ill health and where to begin to design new therapies in the future.
For example, common diseases like high blood pressure can be rooted in problems that occur at a cellular level and eventually have an impact on a whole organ, for instance the heart.
In the journal Structure, molecular biologist Mike Henne, a Phd student in Harvey McMahon’s lab at the Medical Research Council Laboratory of Molecular Biology in Cambridge, unveils the exact make-up of one such cellular structure called the F-BAR domain. This tightly twisted structure helps the cell to fold and crumple the membrane that surrounds it.
A cell’s ability to remodel its membrane is essential for it to function. Henne explains why creating curves is so important: ‘‘Curves and folds in the cell membrane allow it to package a huge amount of machinery into a small space. In addition, processes like cell movement, nutrient uptake, and cell to cell communication depend on reshaping the cell and pinching off small parts of the cell membrane. This allows materials to be passed from one place to another in tiny ‘cargo boxes’ called vesicles.’’
Henne used X-ray crystallography, an experimental technique that uses X-rays to reveal the structure of molecules and proteins, to find out what the exact structure of the F-BAR domain looks like.
He said: ‘‘Cells sculpt a variety of folds into their membranes. Using X-ray crystallography to reveal the three dimensional shape of the F-BAR domain has allowed us to compare it to other structures, for example the banana-shaped structure known as the BAR domain that in comparison creates more extreme curves in cell membranes. Overall, this research has shown how the F-BAR is distantly related to the bendy BAR domain and can use its own shallow crescent shape to coerce the cell membrane into curving.’’
‘‘This variation in domain structure adds to the range of curves cell membranes can form and reveals how these structures guide creation of the many folds and curves that allow the cell to generate and respond to huge demands using a relatively small surface area.’’
The next step is to figure out what role the protein that contains this F-BAR domain has in the cell.
‘‘It is known that several other BAR domain proteins are involved in a process called endocytosis that allows cells to pick up nutrients and other items from their environment. But, F-BAR domains seem to exist on proteins that have a completely different function, those involved in organising the internal structure of the cell, its so-called cytoskeleton. This could mean that different curvatures are required by the cell to organise the different process it undergoes throughout its life-cycle.’’ Henne concludes.
Original research paper: Structure and Analysis of FCHo2 F-BAR Domain: a Dimerising and Membrane Recruitment Module that Effects Membrane Curvature was published online in Structure on 31 May 2007.
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