Proteins in cells are like multi-tasking mothers
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The size and shape of proteins make them versatile
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Of the four major macromolecules in the cell — DNA, RNA, proteins and carbohydrates — it is DNA that has been raised to the pedestal. Granted, DNA carries vital information that the cell needs for its life, but how does it get this information read and processed into action? Through RNA and proteins, respectively.
Genetic information
Despite these important duties of transcribing the genetic information (which RNA does) and translating it into action (which proteins do), these two have not gotten the press they should.
RNA has been dubbed as the “humble carrier of messages and fetcher of building materials”. Proteins have been compared to coolies, doing the donkeywork of keeping living organisms living. Carbohydrates have been treated even worse.
It is only in recent years that the tide has turned. First, came the surprise that RNA comes in various functional types. Some hasten or catalyse chemical reactions, a property that was reserved until then for proteins.
Primordial cell
This discovery led to a change of heart, and an ‘RNA world’ began to be envisaged. In this primordial world, RNA is the genetic material, carrying information digitally in its four-alphabet sequence just as DNA is known to; in addition it also catalyses some vital chemical reactions needed to prime the primordial ‘cell.’
Life before DNA, then, would have been possible with RNA acting as the legislative and executive wings. The 1989 Nobel went to Thomas Cech and Sidney Altman, who showed this double-tasking aspect of RNA.
But RNA would not stop at this. During the last decade, biologists have seen more functions of some short chains of RNA. One of these goes and attaches itself to the RNAs that carry genetic messages, and sets in motion a process that destroys these messengers.
Those interfering pieces of RNA, termed RNAi, have proved to be useful tools to selectively silence chosen genes. Their pioneering work on RNAi fetched Drs, Craig Mello and Anthony Fire last year’s Nobel.
RNA secrets
In the popular press, RNA is the new hero. The June 16th issue of The Economist has spent four pages on RNA, dubbing the Really New Advances in biology coming out of unravelling the secrets of RNA as ‘Biology’s Big Bang.
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Some short chain RNA molecules help keep male fish and flies fertile, others turn off one of the two female X chromosomes, yet others stagger between protein-coding genes and orchestrate the genes in a sequential fashion. It is not quite ‘Move over, DNA’, but ‘Let me in the limelight too’ for RNA.
But in all this excitement and adulation, poor proteins are still waiting in the wings — unhonoured, unsung. Perhaps a more relevant comparison of the cell, in this context, is that of a family.
Multi-taskers
Proteins are like the hassled mother of a busy household; many proteins have always been multi-taskers as most mothers are.
Until about 30 years ago, the mantra was: one gene-one protein and one protein–one function. But evidence was gathering in laboratories that the same protein could perform at least two functions.
One of the earliest examples was an enzyme called PDI. Other than its textbook function of switching the geometry of sulphur-sulphur bonds in other proteins, it was shown to do at least six other functions!
A lucid, readable account was published by Professor T. Ramasarma (of Bangalore and Hyderabad), entitled “one protein-many functions” in the July 1994 issue of Current Science. Since that time, more than 70 proteins have
been documented to do such multi-tasking.
The latest to join the family is the protein called alpha-B crystallin, a component of the mammalian eye lens. Over a dozen such crystallin proteins are seen packed in the eye lens as structural components, just as glass is in the common microscope lens.
During the last 20 years it became known that some of these human lens crystallins (alpha A and B) help other proteins adopt their proper shapes, some others (beta and gamma) serve as depots that store calcium ions, and one of them (beta) even has antibacterial property — all this in addition to their role as the structural material of the lens.
A recent report in Nature (June 13, 2007) describes that alpha-B crystallin acts as a drug, protecting and offering therapeutic effect in mice suffering from a form of nervous system disorder called autoimmune encephalomyelitis. Thi
s adds one more function to this molecule; which has already been shown to be a neuroprotective agent as well an inhibitor of one form of cell death.
What makes proteins so versatile? It is their size and shape. Protein chains are long strings with beads and pendants along the chain.
They can adopt a variety of shapes when the chain folds over itself, offering a three-dimensional structure with crevices, pockets and surface patches into which other molecules can fit in, interact and do chemistry.
It is this structural form that leads to function. Imagine now a protein containing two or more architectural features. One of them might bind or ‘receive’ a guest molecule (substrate) and chemically react with it producing a product.
The second structural domain could bind or interact with a different substrate and do something else. It is this structural feature that allows for multiple functions.
Indeed, it is this same feature of structural domains, pockets and patches that allows RNA molecules to do multi-tasking. In contrast to proteins and RNA, the DNA molecule is prosaic.
It adopts the shape of a spiral staircase; rather dull with little three-dimensional diversity. Yes, there is the odd DNA that does have some, and hence shows some enzyme-like activity but by and large the beautiful double helix leaves DNA with little multitasking ability.
Professor Ramasarma is a protein pundit, and picky with prose. When some others described multiple-task proteins with loose terms, he balked.
Original definition
He titled his Dec 10, 1999 review in Current Science thus: “Is it fair to describe a protein recruited for many cellular chores as moon lighting and promiscuous?” Apparently, the original definition of a moonlighter was
one of a band of cowardly ruffians who committed agrarian outrages by night.
The current colloquialism refers to one who holds two jobs, often (but not essentially) one of those at night. Even so, I hesitate, as an eye biologist, to club alpha-B crystallin (or any protein for that matter) as a moonlighter.
D. Balasubramanian
dbala@lvpei.org
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