Intermediate Physics for Medicine and Biology: Aquaporins and Peter Agre

Friday, May 13, 2022

Aquaporins and Peter Agre

In Chapter 5 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I mention aquaporins, a type of membrane channel. In a footnote, we write

Some aquaporins are permeable only to water, and not to any other small molecules or ions, even hydrogen ions (Preston et al. 1992). Aquaporins are formed by proteins that span the cell membrane. Their structure has been determined by x-ray crystallography (Murara et al. 2000). Their selectivity arises from a narrowing of the channel to about 0.3 nm, about the size of a single water molecule. Aquaporins allow water to cross cell membranes at a much higher rate than it could diffuse through. Genetically defective aquaporins may be responsible for some clinical diseases, such as nephrogenic diabetes insipidus and congenital cataracts (Agre et al. 2002).

In 2003, Peter Agre was awarded the Nobel Prize in Chemistry for the discovery of aquaporins. My goal in this post is to provide a bit more detail about aquaporins and Agre.

To learn more about these water channels, let’s begin with this simple, fun Claymation video.

Claymation video about aquaporins by Sophia Dudte.
https://www.youtube.com/watch?v=7EGPtMqZ7pY

Next is a more rigorous simulation of an aquaporin

A simulation of a water channel in a cell membrane, performed by The Theoretical and Biophysics Group at the NIH Center for Macromolecular Modeling and Bioinformatics.
https://www.youtube.com/watch?v=GSi5-y6NHjY

Russ and I cite the paper by Murara et al. (2000). The full citation is

Murata K, Mitsuoka K, Hirai T, Walz T, Agre P, Heymann JB, Engel A, Fujiyoshi Y (2000) Structural determinants of water permeation through aquaporin-1. Nature, Volume 407, Pages 599–605.

The abstract is listed below.

Human red cell AQP1 is the first functionally defined member of the aquaporin family of membrane water channels. Here we describe an atomic model of AQP1 at 3.8 Å resolution from electron crystallographic data. Multiple highly conserved amino-acid residues stabilize the novel fold of AQP1. The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport, whereas the water selectivity is due to a constriction of the pore diameter to about 3 Å over a span of one residue. The atomic model provides a possible molecular explanation to a longstanding puzzle in physiology—how membranes can be freely permeable to water but impermeable to protons.

Below is a illustration of the aquaporin molecule. The view is perpendicular to the membrane, and the little hole in the middle is the pore.

Illustration of an aquaporin molecule. Drawn by David Goodsell.

Next is the introduction to the Wikipedia article about Agre (references removed).

Peter Agre /ˈɑːɡriː/ (born January 30, 1949) is an American physician, Nobel Laureate, and molecular biologist, Bloomberg Distinguished Professor at the Johns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, and director of the Johns Hopkins Malaria Research Institute. In 2003, Agre and Roderick MacKinnon shared the 2003 Nobel Prize in Chemistry for "discoveries concerning channels in cell membranes." Agre was recognized for his discovery of aquaporin water channels. Aquaporins are water-channel proteins that move water molecules through the cell membrane. In 2009, Agre was elected president of the American Association for the Advancement of Science (AAAS) and became active in science diplomacy.

You can learn more about Agre in the videos below.