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After a protein has been synthesized and its the final tertiary/quartenary adopted, how does it reach its substrate within the cell and what causes it to interact with it?

The transcription factors for a particular gene are proteins which are translated from genes on some other portion of the DNA. (That happens in the cytoplasm) But how do the transcription factors know that it has to diffuse into DNA region of the nucleus.

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  • $\begingroup$ proteins as well as other small molecules like pharmaceuticals and steroid hormones all bind with specificity for particular targets within the cell - this specificity is what makes the protein seem like it wants to seek out its target - I'm sure there are more chemical-minded individuals that can give you a good explanation about binding energy and exergonic reactions, etc - good quesetion $\endgroup$ – Vance L Albaugh May 22 '16 at 20:57
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    $\begingroup$ A protein doesn't "know" anything, just like gravity doesn't "know" anything. There are all kinds of proteins as well; there are cell receptors, carrier proteins, cytoplasmic enzymes, structural proteins, etc. Are you specifically asking about enzymes and substrates? Or generally how do proteins "know" what to do? $\endgroup$ – anongoodnurse May 22 '16 at 21:08
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    $\begingroup$ As a side note, we don't know anything as per the Central Dogma. The Central Dogma was a model, not a set of observations, not even a hypothesis; it was deliberately named to be provocative, and was overthrown pretty quickly. It's a mere footnote to history, not an important biological concept. Unfortunately, there seem to be a group of teachers -- mainly in India -- who don't understand this, who force it onto students, and who put it on exams, leading to widespread misunderstanding. $\endgroup$ – iayork May 23 '16 at 11:54
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The protein doesn't move towards anything. It just randomly diffuses (bounces around) in the cell until it sticks to something. The particular chemical structure (the shape) of the protein and whatever it hits will determine how tightly they stick together and whether or not a chemical reaction occurs.

A way to imagine this is to think of a jar filled with a lot of glass marbles (water), 1 marble shaped magnet (the protein), and 1 metal marble (the substrate). Put the magnet at the bottom, fill the jar most of the way full with glass marbles, and then put the metal marble on top. Then close the jar and shake it. Eventually, after colliding with a lot of glass marbles, the magnet and the metal marble will collide and stick to each other. That's how it works in cells also. In cells, the speed at which the molecules move is proportional to temperature.

Here's a cool video that shows how proteins with a very specific shape bouncing around randomly can assemble into a complex structure.

To get a sense of just how quickly molecules move in a cell, think of a bacterial cell. An E. coli cell is about 1 micrometer in diameter. In a cell of that size with no sub-cellular compartments, every molecule will collide with every other molecule in the cell about once every second (if we make some assumptions such as no binding to other molecules). So if the cell contains just one unit of a certain enzyme, and just one molecule of its substrate, they will still collide fairly frequently (about once every second).

This rate decreases dramatically as radius of the cell increases. For example a cell with double the diameter (2 micrometers) has a volume eight times larger, so collisions between any two molecules take 8 times ($2^3$) as long to occur (in other words, it takes molecules 8 times longer to "find" each other). This is one reason why there is a kind of upper limit on the size of an individual cell. Bigger organisms are bigger because they have more cells, not because they have larger cells.

The field of biology concerned with how likely it is for a reaction to occur is called enzyme kinetics. A related field, which deals with how frequently molecules collide is called statistical mechanics.

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    $\begingroup$ It just randomly diffuses in the cell until it sticks to something. This isn't entirely accurate. The secretory system can deliver proteins to specific parts of the cell and then some are embedded in the membrane whilst others have signal peptides which can be cleaved off, releasing the protein into the local vicinity. Motor proteins are even involved in the final stages of this, making it a particularly directed process. Furthermore, could you provide a reference supporting that as a reason for the upper limit of cell size? $\endgroup$ – James May 23 '16 at 3:29
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    $\begingroup$ You're right of course. I should have stipulated that this applies best to soluble, cytosolic proteins. I would argue however, that what you're describing with secretory processes, is just a special case of diffusing around randomly until it sticks to something. In the case of secretory pathways it's just that there's a cascade, where once it interacts (sticks) to the first other protein in the cascade, it forms a complex that interacts differently than any of the two precursor proteins. And so on as the cascade hits different steps. It's just a bunch of molecules randomly bouncing around. $\endgroup$ – Sean Johnson May 23 '16 at 5:51
  • $\begingroup$ As far as a reference for cell size. I think I heard that in a class or read it in a text book a long time ago. Quickly looking around the Internet, I found a reference that is sort of sufficient (it doesn't account for eukaryotic cells, just bacteria). Here's that. $\endgroup$ – Sean Johnson May 23 '16 at 6:29
  • $\begingroup$ @SeanJohnson I understand your implications of statistical mechanics to chemical interactions inside the cell in order to reach a binding affinity that is sufficient to keep the molecules together. But as I had mentioned about transcription factors in my question, I am not able to correlate it exactly. The transcription factors' activity is within the nucleus. In that case how would it travel inside through the nuclear membrane? I am unable to understand how would it be a random interaction if it has to specifically penetrate the membrane to reach its target. $\endgroup$ – Synaptic_Pik May 23 '16 at 19:18
  • $\begingroup$ So your question is more about how proteins in eukaryotic cells enter various sub-cellular compartments? Or is it more about what distinguishes the outer membranes of different compartments? Check out the Wikipedia article about "nuclear pores" $\endgroup$ – Sean Johnson May 23 '16 at 20:29

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