The Signal Recognition Particle

Let’s sketch out the basic events associated with getting a protein across the membrane.  We’ll join the story after the gene for this protein has been expressed and an RNA molecule coding the amino acid sequence is synthesized.  This RNA is known as messenger RNA (mRNA) and it is ultimately fed into the ribosome where its sequence of nucleotides will be decoded and used to string together a particular sequence of amino acids.   (see animation here).

srp

Figure 1.  The first half of the signal recognition particle pathway known as elongation arrest.

Figure 1 shows a simplified representation of some of the players involved in this drama. The mRNA that is threaded into the ribosome is not shown.  But what you can see from Figure 1a is a small “window” where the tRNA (also known as transfer RNA) and elongation factor enter the ribosome.  The tRNA carries a specific amino acid that will correspond to a specific codon sequence on the mRNA.  The elongation factor will guide the tRNA to the proper arena within the ribosome for this interaction to occur.  Thus, as the ribosome reads the string of nucleotides on the mRNA, a stream of elongation factors/tRNA pour into the ribosome to hand over the specified amino acids.  As synthesis proceeds, the growing chain of amino acids emerges from an exit tunnel (the “window” on the bottom left of the ribosome in Figure 1a).

Now, here’s the catch. If the newly forming protein is destined for secretion (or insertion into the membrane), the first amino acids to emerge from the ribosome will contain a positively charged amino acid followed by about 10-20 hydrophobic amino acids.   This characteristic arrangement constitutes the signal sequence which in turn will be recognized by the signal recognition particle (SRP).

matrix2In human cells, the SRP is composed of an RNA molecule, about 300 nucleotides in length, attached to six different proteins.  Four of the proteins bind to one end of the RNA and form the so-called S domain, a region of the SRP that binds near the exit tunnel as shown in figure 1a.  The other two proteins bind to the other end of the RNA and form the Alu domain.  When the signal sequence emerges from the exit tunnel of the RNA, the entire SRP complex undergoes a shape change that allows the Alu domain to attach to the window where the tRNAs enter the ribosome.  The resulting complex temporarily pauses protein synthesis  (Figure 1b).

Once protein synthesis has been paused, the complex formed from the ribosome, the signal sequence, and the SRP will then dock into a receptor on the membrane (Figure 2).

srp2

Figure 2.  The second half of the signal recognition particle pathway.

The S domain from the SRP interacts with this receptor, causing the SRP to let go of the signal signal sequence.  The ensuing shape change also causes the Alu domain to move away from the tRNA window (Figure 2a) and now protein synthesis can resume.  However, now the exit tunnel is positioned right next to a membrane channel known as the translocon.  When the ribosome resumes protein synthesis, the newly forming amino acid chain is threaded into the tunnel provided by the translocon, allow the protein to pass through the membrane.  The whole process is also coordinated with the GTP molecule, which is very similar to ATP.  Upon binding to each other, both the SRP and its receptor also bind GTP and then break it down.  Once the GTP has been broken down, the energy released will allow the SRP and its receptor split apart and the SRP dissociates from the ribosome where it can be reused with another ribosome.

The story thus ends with the ribosome snapped on to the translocon, pumping its newly made protein across the cell membrane while the SRP is released for use by another ribosome looking to secrete its protein product across the membrane.

Would you like to  learn more?

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2 responses to “The Signal Recognition Particle

  1. Pingback: The SRP, Alu Elements, and Nudging «

  2. Thank you for this! It really helped me understand the role of SRP and what it actually is!! Loved this!

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