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Aquaporin and the Cambridge Five

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made using VMD

Sometimes analogies go a long way, surprisingly long.  Aquaporins are ubiquitous water channels in living cells, known to be tetrameric, each unit contributing one pore.  This much is certain and this is where an analogy begins, namely with a British spy ring that passed information to the Soviet Union during world war II and into the 1950s.  The ring is often referred to as the Cambridge Four since the spies, when recruited, were undergrads at Cambridge Trinity College and there were four of them (cryptonyms Stanley, Homer, Hicks, and Johnson).  But a Fifth Man was long suspected, yet never formally identified. Here the analogy continues: aquaporin was suspected to sport a fifth pore, supposedly at its center, where its four subunits join (hence known as the tetrameric pore).  Strong, but not yet completely conclusive,  evidence has now been put forward in a recent report that the central pore, actually quite plainly visible to the eye when aquaporins are inspected by molecular graphics, e.g., with VMD, is an ion channel gated by a common cellular signaling molecule, cGMP. The evidence stems from a combined computational (molecular dynamics using NAMD) and experimental (verifying computationally suggested mutants) study.  More information on the five pores can be found on our aquaporin website, more on the Cambridge Five here. But the analogy goes further. Today it is suspected that the Cambridge Five actually had more than five members and the same holds for the pores of aquaporin.  An ongoing investigation has lead to evidence that the further pore members conduct gases, for example carbon dioxide.  Hopefully, we will know one day with certainty all members of the Cambridge Five and all pores of aquaporin.