Cell Membrane Has Ticket-Operated Turnstiles
Cells are like castles surrounded by walls. A wall without gates, however, would prevent commerce and trap the inhabitants inside. The cell has ingenious gates that control the flow of goods and services through its outer membrane under tight surveillance and quality control. This controlled flow, as opposed to passive diffusion or osmosis, is termed active transport. Depending on the type of import or export required, the cell uses a variety of mechanisms. It might wrap the cargo in clathrin proteins and send it through in a self-mending breach of the walls (endocytosis; 05/15/2005, 11/04/2005, bullet 7). It might use one of the specialized authenticating channels through the membrane (e.g., aquaporins 04/18/2002 and ion channels, 05/29/2002). It might export genetic material or proteins through one of the pumps, or secretion systems (10/11/2005, 11/10/2004). Or, it might check cargo through one of the varieties of self-operating ticketed turnstiles.
A description of one of these gates excited awe in a commentary in PNAS.1 Robert M. Stroud summarized decades of work on a kind of lactose turnstile. Key researchers published their latest results in the current issue of the journal. They believe they have finally figured out how this molecule-sized machine works. It is a protein, 417 amino acids long, folded into a kind of rocking door in the membrane. For a lactose passenger to get through the membrane using this transporter, it has to pay the fare: a proton ticket must first be inserted into the active site. Then, the lactose molecule gets in and fastens its seat belt, so to speak, for the short but wild ride. The nanomachine undergoes a conformational change that seals off the outside and opens the door to the inside, where the passengers undock. Then, the gate automatically repositions itself for the next load. Called LacY, or lactose permease, this molecular machine operates with practically 100% efficiency: each proton ticket grants admittance to one and only one lactose passenger.
LacY is one of a whole family of gates called the “Major Facilitator Superfamily” (MFS).2 “The mechanism most probably pertains to the many other transporters of the MFS that are found throughout all domains of life,” Stroud says. Another member of this family, for instance, is called GlpT. This machine works with a reverse-ticketing process; a phosphate outside the cell is exchanged for a glycerol phosphate inside.
Stroud was palpably delighted with the elucidation of the mechanism of these intriguing nanomachines after so much research by so many scientists for so many years. Here’s what he said about the LacY device:
The MFS of transporters can be run in reverse, such that outward movement of lactose, driven by reverse concentration gradient, can generate an H+ gradient across the membrane; LacY can work in either direction toward a coupled equilibrium. It is a beautiful example of energy transduction at the level of the membrane and is a near-perfect machine in the sense that the stoichiometry3 is always 1:1 without any leakage.
Leakage would allow contraband through. Experimental inventory shows all goods accounted for, before and after. The protein undergoes “large global conformational changes to transport the cargo” that are reversible, providing “oscillation between structural states that become accessible alternately to one side or the other, which can therefore be coupled to other sources of energy.”
Understanding how these machines work could lead to treatments for diseases, such as cystic fibrosis and lactose malabsorption, caused by malfunction of the gates. In addition, medical researchers may discover novel ways to co-opt the gates for special delivery of antibiotics and chemotherapeutic drugs.
1Robert M. Stroud, “Transmembrane transporters: An open and closed case,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0610349104, published online before print January 24, 2007.
2Another superfamily of transporters, the ATP Binding Cassette (ABC) family, is driven by ATP hydrolysis inside the cell.
2Stoichiometry refers to the ratios of combining elements in a chemical reaction, from the Greek stoichea, “basic principles,” as used in Colossians 2:8.
Wonderful, amazing, mind-boggling discoveries come from the investigation of design in nature. Stroud said nothing about how these machines arose by evolution; indeed, he said these mechanisms are “found throughout all domains of life.” Moreover, this particular 100%-efficient machine is made up of 417 amino acids. Our online book calculates the probability for a 400-amino-acid protein arising by chance as one in 10161. This unfathomably low probability rules out its formation by any lucky accident in trillions upon trillions of universes (ch. 7).
The LacY protein machine cannot tolerate much error, either. One primary method the scientists use to learn about them is by replacing amino acids with the wrong ones, and watching how the machines break.
From the top of the giraffe to the lowly crocus, molecular machines transduce life within a physical medium. This is no hocus, folkus. This is intelligent design coming into focus – at the locus of mind and matter, at the intersection of faith and reason. Let the NCSE run for cover, wailing, “Cloak us from the face of ID, for the facts emerging from biophysics provoke us to shame and despair.” Rejoice, O science, as the lens of molecular biology leads to a refocus on intelligent design.