CHEMICAL & ENGINEERING
NEWS OF THE WEEK SEPTEMBER 1 \L 2Û04 - EDITED BY WILLIAM G. SCHULZ & JANIET $. DODO
through the tunnel, Stroud notes. The channel's ability to discriminate against NH4+ is crucial because the protein must not alter the charge bal ance across the mem brane by mistakenly letting K+ or other cat 3 ions through. Indeed, FAMILY O F M E M B R A N E 1.35 Â, an unprecedented level of Stroud's team has con spanning proteins that resolution for a membrane-span- firmed that the chan mediate gas transport has ning protein. The structure re- nel conducts NH3— finally yielded its secrets. Scien- veals that the channel is made up and not ammonium tists at the University of Califor- of three identical membrane- ion—via a fluorescence nia, San Francisco, have used X- spanning subunits, each ofwhich assay using channelray crystallography to reveal the contains a 20-Â-long hydropho- studded vesicles load molecular architecture of a bac- bic tunnel just wide enough for ed with a pH-sensitive terial protein that ushers ammo- NH 3 molecules to pass through fluorescent dye. nia across cell membranes [Sci- singlefile.Wider vestibules flank The mechanistic in ence, 305,1587 (2004)1 each end of this narrow tunnel. sights provided by the GAS FILTER Aromatic Stroud suggests that the con- structure of this bacte This structure—thefirstofany residues (blue) lining the gas channel protein—provides "a stellation of aromatic residues in rial ammonia channel channel's extracellular quantum leap forward in our un- the extracellular vestibule binds are likely to shed light vestibule stabilize NH4+. But derstanding of gas transport," ammonium ions from solution on the workings of its only NH3 molecules can note biochemists Peter Agre via π-cation interactions. In this human cousins, Stroud of Johns Hopkins University vestibule, it appears that ammo says. Those relatives in continue through the narrow hydrophobic tunnel, thanks School of Medicine and Mark A. nium ions are converted to am clude the Rh blood to weak C-H--N hydrogen Knepper of the National Insti- monia molecules. In the narrow group proteins found tutes of Health in an accompany- tunnel beyond the vestibule, two on red blood cells — bonds donated by a pair of conserved histidines (red). histidine residues poking out of which are reported to ing Science commentary These NH3 molecules are ferry both ammonia Ammonia is a gas, but in aqueprotonated to give NH4+ and carbon dioxide ous solution it exists predomi+ when they reach the inner across the cell mem nantly as ammonium ion (NH4 ). vestibule. brane—as well as a Bacteria use ammonia as a nitronumber of physiologi gen source to make amino acids. cally important ammonia chan In humans, ammonia is an imnels that regulate body pH and portant reactant in a variety ofreprotect against ammonia tox actions. Although this crucial icity Stroud suggests that molecule can slowly diffuse the structure might be through cell membranes on used to understand the its own, nearly all organisms molecular basis of diseases contain membrane-spanning caused by ammonia toxicity channel proteins that allow amand perhaps even to design monia to cross the lipid bilayer drugs to treat them.—AMANDA in a rapid and controlled manner. YARNELL Professor Robert M. Stroud, postdoc Shahram Khademi, and their coworkers in the biochem- the tunnel's waxy wall stabilize TUNNEL VISION Each of the protein's three istry and biophysics department the N H 3 molecules via weak identical subunits contains a tunnel that guides NH3 at UC San Francisco have now C - H - N hydrogen bonds. Be across the cell membrane. Three NH3 molecules (blue) solved the structure of a model cause NH 4 + ions can't accept any are in each tunnel, while NH4* molecules (orange) bacterial ammonia channel to hydrogen bonds, they cannot pass remain near the tunnels' entrances.
BIOCHEMISTRY
CHANNEL PROTEIN STEERS GAS
X-ray structure reveals how protein ushers N H across cell membranes
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C & E N / S E P T E M B E R 13, 2004
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