Tuesday 28 October 2014

If proteins were in my wardrobe: folding and organisation

So my blog has been very quiet (apologies). A new start to the academic year so a new blog post!


When you open your wardrobe, how does it look?
Like this?
(1) Clean and tidy









...Or admittedly more like this?
(2) Disorganized and messy


Many things in molecular cell biology can appear rather chaotic on the surface. Proteins look like highly higgledy piggledy molecules. When  actually they’re pretty organised things: structurally complex and sophisticated molecules of life.

How the cell folds its wardrobe


Amino acid sequence: The shape of a protein is determined by its amino acid sequence (primary structure)- the threads of the garments (20 types in total). They can be grouped into different categories according to their side chains-acidic, basic, uncharged polar and nonpolar.

(3) 20 Amino acids 


Non covalent bonds also influence the folding of proteins: hydrogen bonds, ionic bonds and Van der Waals attractions.

Environment: The cell has a very aqueous environment which affects a proteins shape, making it very compact. The non polar side chains are hydrophobic (water-fearing) bury themselves in the core of the proteins whilst the polar (hydrophilic- water-loving) side chains interact with water and so tend to gather on the outside of the protein.

When completing a task we often look for the easiest way to accomplish the task with minimal cost (whatever that may be) Proteins do the same: they fold into a shape of the lowest energy (i.e energetically favourable to maintain- the easiest way to fold).

Organisation of protein structure

Unlike my wardrobe proteins have a very organised structure that can be broken down into four categories:
(4) Categories of protein structure 

Many proteins have large structures (of one very long string on amino acids folded up) which gives a further unit of organisation: the protein domain.

 This is a length of the protein which is between 40 and 350 amino acids (stitches) in length. This length folds independently to the other regions of the protein like different parts of a shirt (collar, sleeve,  the pocket) are all still part of one shirt but and useless on their own yet still independent.
Different protein domains often are associated with different functions.

Items in a cells wardrobe (some examples)


Src protein kinase:  One of the many secretaries of the cell. It acts in signalling cascades by adding phosphate groups from high energy donor molecules like ATP to substrate molecules.
A protein formed of four different domains (each has a different function).

The SH2 and SH3 domains are involved in regulation whilst the catalytic domain and the activation loop play a role in the catalytic activity of the kinase.

(5) Src Kinase Hck


Haemoglobin: Found in red blood cells and vital for the transport of oxygen around the body and also has roles in the transport of carbon dioxide and hydrogen ions. It is a multi-subunit protein: two α subunits (two protein chains of 141 amino acids-stitches) and two β subunit (two protein chains of 146 amino acids-stitches).

(6) Haemoglobin
So next time you open your wardrobe to put your clean clothes away (freshly synthesized (nascent) proteins) think about how organised our cells are: folding proteins and packaging them to be sent to various locations within the cell. How organised is your wardrobe?

Upcoming posts
More about protein organisation and folding-why and the cellular machinery involved
What happens when folding goes wrong?

References
Alberts B et al., 2008., 5th Ed., Molecular biology of the cell., New York., Garland Science
Berg  J et al., 2011., 7th Ed., Biochemistry., New York, W. H. Freeman

Images


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