Amazing Proteins

All living things depend on proteins. Yet I sometimes wonder just how many people pause to consider just how amazing proteins are. Consider your own body. If you dig deep enough, it’s often as if a major organ system is centered around the function of a protein or small subset of proteins. Your muscles? Think of actin and myosin, the contractile proteins. Your brain and nerves? Think of the membrane receptors and channels that generate and transmit electrical signals. Your blood? Think of the hemoglobin that transports oxygen. Your digestive system? Think of the enzymes that break down all the food molecules (which, of course, include proteins). Your bones and joints? Think of collagen that binds things together. Your skin and hair? Think of that tough protein, keratin. Your glands? Think of hormones and the receptors that detect them. Your immune system? Think of the antibodies that guard your body.

See proteins as design material and suddenly you are struck by their immense versatility, as if they represent the ultimate, all-purpose substance for generating function.

They can generate light, detect light, or use light to generate ion gradients and chemical energy. They can act as a signal or detect a signal. They can impart movement and function as motors. You can use them to bind things together and to unbind things. They can be used to catalyze thousands of chemical reactions, transport tiny or bulky molecules, transmit signals across great distances, and/or proofread. They can exist as everything from a simple fiber to a complex, sophisticated molecular machine. They can function alone or as part of a circuit. Combine them with lipids, and you have a controllable barrier, perfect for compartmentalization. Combine them with DNA and you have a chromosome that can be regulated and packaged. Combine them with RNA and you have machines that can make proteins and perfectly splice genes. You can use them to evolve things, as the deeply influential processes of gene duplication, recombination, and horizontal gene transfer are dependent on, you guessed it, proteins. You can even use proteins to form the hard turtle shell, soft bunny fur, and the flight feathers of a duck.

Particle Protein and Friends

To really appreciate the beauty of the SRP system, we should look more closely at the major players.  But first, let’s make things more manageable.  Lucky for us, the bacterium E. coli has a scaled-down version of the system that nevertheless functions much like the system seen in human cells [8].  The RNA is much smaller, being only 114 nucleotides in length and thus lacking the Alu domain [9].  Furthermore, instead of having six different proteins as part of the SRP, the E. coli version has only one, known as Ffh.  Since there is only one, we’ll just call Ffh the ‘particle protein.’  E. coli also has the receptor (FtsY) and the translocon (SecY).  Thus, the system is actually quite simple, being composed of a small RNA molecule (4.5S RNA) that is bound by the particle protein which in turn binds to the receptor and the translocon.

Let’s first put the particle protein under the microscope.

Alpha Bunny

Some see a yapping dog.

Smart folks see a rabbit keeping the dog where he belongs.

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).

Word Frequency

There’s a neat little tool you can use called the Word Frequency Counter. It can provide a nice snapshot of the concepts and terms any particular writer finds important.  So, out of curiosity,  I decided to combine these 14 essays and see what came out of the analysis.

The Charybdis

Carl Woese has co-authored another thought-provoking article entitled, How the Microbial World Saved Evolution from the Scylla of Molecular Biology and the Charybdis of the Modern Synthesis.  He makes several startling claims, including:

As for evolution, it had been developed from a phenomenological description centering around what was generally termed natural selection into the modern evolutionary synthesis through its union with Mendelian genetics. The modern evolutionary synthesis should have been the 20th century’s evolutionary bastion, the forefront of research into the evolutionary process. No such luck!

The basic understanding of evolution, considered as a process, did not advance at all under its tutelage. The presumed fundamental explanation of the evolutionary process, “natural selection,” went unchanged and unchallenged from one end of the 20th century to the other. Was this because there was nothing more to understand about the nature of the evolutionary process? Hardly! Instead, the focus was not the study of the evolutionary process so much as the care and tending of the modern synthesis. Safeguarding an old concept, protecting “truths too fragile to bear translation” is scientific anathema. (The quote here is Alfred North Whitehead’s, and it continues thus: “A science which hesitates to forget its founders is lost” [32].) What makes the treatment of evolution by biologists of the last century insufferable scientifically is not the modern synthesis per se. Rather, it is the fact that molecular biology accepted the synthesis as a complete theory unquestioningly—thereby giving the impression that evolution was essentially a solved scientific problem with its roots lying only within the molecular paradigm.

There you have it. An entire century spent studying biology without seriously addressing evolution, without assigning importance to the study of the evolutionary process. Our understanding of biology, of biological organization, far from being near complete (as molecularists would have us believe), seems still in its infancy.

Ribosome Enigma

If we are about to explore the signal recognition particle through the telic lens, it might help some people to familiarize themselves with the molecular machine known as the ribosome.  So sit back and enjoy the protein synthesis show.

Connections

Life is a balancing act existing at the interface of opposing demands.  This realization comes from many directions and even finds itself entwined within the pillars of PICERAS.  As we saw earlier, PICERAS represents the seven universal pillars, or themes, found in all living cells.  One of these themes was Compartmentalization, where it is important to sequester the contents of the cell from its external environment, thereby allowing the cell to maintain an internal state that is completely different from the outside.  To compartmentalize the contents, we require a barrier that effectively cuts off all the internal activity of the cell from its outer environment.   But this poses a problem for other elements of PICERAS.  Adaptability, for example, is the process whereby cells communicate with the environment and respond to it in order to maintain their internal states.  If the cell was completely cut off from its environment, how could it detect and respond to it?  Furthermore, the pillar of Improvisation will work best if cells can communicate with their environment, evolving new solutions to the problems posed by this very environment the cell contents must be protected from.  So on one hand, the cell needs to be left alone, but on the other hand, the cell needs to be plugged in.  Shall it be an introvert or an extrovert?  Actually, the cell doesn’t have to choose because it has a very special “skin” – the membrane.

Inspector Rabbit Does it Again

Whoa!  Inspector Rabbit has found one juicy lil’ nudgin’ nugget.  Yummy. It’s goin’ take a series of essays to lay it out and connect some very interesting dots (or should I say, puffs?).  As the story develops, it gets better and better with multiple layers of telic echoes.  And when it’s all done, I’ll combine them into one huge essay for future reference (as no one else has made these connections).

You’ll know which essays to connect whenever you spot Insp. Rabbit with his new find.

Predictable evolution

Let’s finish up with some excerpts from Adam Wikins’s paper, “Between ‘‘design’’ and ‘‘bricolage’’: Genetic networks, levels of selection, and adaptive evolution” (PNAS 2007  vol. 104, pp. 8591-8596).  We have seen two levels of constraint on the “choice” of evolutionary trajectories: 1) the set of preexisting properties of the recruited molecule and 2) the recruited gene must be expressed in the appropriate context.  Wilkins next points out that such cooption often rises above the level of the gene and involves modules: