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technical achievement: it is the highest-resolu-tion structure ever produced from electroncrystallography, and only the second to show the lipid environment of a membraneprotein. The other structure showing this is of bacteriorhodopsin from the purple mem-branes of a photosynthetic bacterium3.

Walz and colleagues’ structure shows theAQP0 molecules in their closed form, orga-nized as complexes of four AQP0 units(tetramers) in each lipid bilayer. The flat extra-cellular surface of a tetramer in one bilayercontacts the extracellular surface of anotherAQP0 tetramer in the adjacent bilayer. This‘head-to-head’ packing links the two adjacentbilayers to form a structure that looks very likean in vivo cell–cell junction4.

The artificial lipid bilayer is made ofdimyristoylphosphatidylcholine, a moleculewith a ‘head’ containing a negatively chargedphosphate group and a positively chargedcholine group, and two ‘tails’ of fatty acyl

chains, each with 14 carbons. InWalz and colleagues’ structure, the lipids can be seen forming ashell around each AQP0 tetramer(Fig. 1). The tetramers are sepa-rated by a shell of lipid molecules,just one molecule thick. Thismakes the lipid molecules unusualin that most are in contact withtwo protein molecules, one fromeach of the adjacent tetramers.

Perhaps this partly explains whyso many of the lipid molecules areresolved in the structure. In theonly other high-resolution struc-ture showing a large number oflipid molecules, that of bacterio-rhodopsin, lipid molecules simi-larly mediate ordered packing ofthe protein molecules, in this caseof trimers of bacteriorhodopsin3.The crystalline array of closelypacked AQP0 tetramers seen inthese reconstituted systems is verylike that seen in the native lensfibre membrane5.

The striking thing about thestructure of AQP0 is the excellentpacking of the lipid fatty acylchains against the rough surface ofthe AQP0 molecule. For somelipid molecules, this is achievedwith almost straight (all-trans)fatty acyl chains, but for othersconsiderable distortion of the

chains is necessary for them to wrap aroundthe bulky side-chains of the protein (Fig. 1).The lipid headgroup conformations also differmarkedly between the various lipid moleculeswith some lipid headgroups being orientedalmost parallel to the surface of the mem-brane, as occurs in crystals of phosphatidyl-cholines6, but with others being orientedalmost vertically.

What the structure makes clear is that theAQP0 surface is not covered by a set of uni-form binding sites for phospholipid molecules.The binding of lipids to AQP0 is therefore veryunlike the interactions between many otherphospholipids and proteins, where particularlipids bind to unique binding sites on the surface of the protein, a classic example being the highly specific binding of phosphatidyl-inositols to protein domains called PHdomains. Rather, the picture presented is of anumber of phospholipid molecules, each withtheir fatty acyl chains interacting with the

CELL BIOLOGY

A greasy gripAnthony G. Lee

How do the lipids and proteins of the cell membrane interact to create a functioning barrier for the cell? A high-resolution structure of a membrane protein reveals intimate contacts with its lipid neighbours.

The design of a biological mem-brane is beautifully simple: a lipidbilayer provides the basic barrier,and into this are plugged a varietyof membrane proteins. Each pro-tein is designed to carry out someparticular function for the cell —moving specific molecules in orout of the cell, say, or sensing theenvironment. The trick is to makesure that the lipid bilayer and themembrane proteins are mutuallycompatible: the proteins must beable to operate well in the environ-ment provided by the lipid bilayer,and insertion of the proteins intothe bilayer must not make it leaky,or the permeability barrier wouldbe destroyed. In other words, thekey to an effective membrane is toget the packing of the lipids andproteins right. On page 633 of thisissue, Walz and colleagues1 presenthigh-resolution structural datathat clearly illustrate how thispacking is achieved.

Thirty years ago, studies of bio-logical membranes using electronspin resonance detected a popula-tion of lipid molecules whose fattyacyl chains were conformationallydisordered2. These chains werethought to belong to the lipid mol-ecules — called boundary orannular lipids — that contactedmembrane proteins. But not everyone wasconvinced, hence the significance of Walz andcolleagues’ work; nothing is as compelling asactually seeing something with your own eyes.

The authors have used electron crystallog-raphy to determine the structure of a proteincalled lens-specific aquaporin-0 (AQP0) whenit is immersed in an artificial lipid bilayer1.AQP0 is the most abundant protein in theplasma membranes of the fibre cells that makeup the bulk of the lens in the human eye. Func-tionally, AQP0 mediates rapid movement ofwater into and out of the fibre cells, but it alsohas a structural role, forming membrane junc-tions between fibre cells. Under the right con-ditions (when at least a fraction of the AQP0molecules are partially proteolytically cleaved)the AQP0–lipid-bilayer system forms two-dimensional crystals consisting of a pair ofclosely spaced membranes.

The structure that Walz and colleaguesobtained from these crystals is a remarkable

Figure 1 | Annular lipids. A side view of the electron crystallographicstructure reported by Walz and colleagues1 showing one face of the AQP0tetramer with lipid molecules forming a bilayer shell around the protein.The AQP0 tetramer is shown as a surface plot (the lighter backgroundmolecule), with red representing regions of negative charge, blue, regions ofpositive charge, and grey, uncharged regions. The lipid molecules are shownin space-fill format (the molecules in the foreground). The charged lipidheadgroups (oxygen, red; phosphorus, orange) and the lipid fatty acyl chains form a bilayer with almost uniform thickness around the protein.Presumably, in the membrane, lipid fatty acyl chains will cover the whole of the hydrophobic surface of the protein; only the most ordered of the lipidmolecules will be resolved in the crystallographic structure.

Inside cell

Outside cell

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large, rough, hydrophobic surface of the pro-tein; their charged headgroups interact withthe charged residues flanking the hydrophobicsurface. Another interesting feature of thestructure is that the thickness of the lipidbilayer around the AQP0 tetramer is ratheruniform, despite the fact that the structuresadopted by the individual lipid molecules arevery different. The lipid bilayer observedwithin the recently published structure ofanother membrane protein similarly seems tobe of constant thickness7.

The picture given here is, of course, of amembrane frozen in time — the structure wasdetermined at low temperature. At normaltemperatures the lipid bilayer would be more fluid; lipid molecules would probably be rapidly entering and leaving the annularshells around the protein molecules, and theencounter between a particular lipid moleculeand a particular protein molecule would bebrief 8. Nevertheless, the structures adopted bythe lipid molecules when they are on the pro-tein surface would be much like those picturedhere, and fast swapping of lipid moleculesbetween the annular shell and the bulk lipidbilayer would not change the environment‘experienced’ by the protein. The proteinwould always experience lipid molecules inthe disordered states shown in the structure ofWalz and colleagues1.

Crystalline membranes of AQP0 can beformed with a variety of lipids other thandimyristoylphosphatidylcholine1. It mighttherefore be possible to use this system toanswer several questions exercising the mindsof membranologists. If AQP0 were reconsti-tuted with a longer chain lipid, how would thelong fatty acyl chains of the lipid moleculesdistort to ensure that the hydrophobic thickness of the lipid bilayer matched thehydrophobic thickness of the protein? Howwould lipids such as phosphatidylethanol-amine that prefer to form non-bilayer struc-tures interact with AQP0? Would changing thestructure of the lipid result in any change in the structure of the AQP0 molecules? Withanswers to these and similar questions, we canstart to understand how lipid and protein mol-ecules coevolved to form membranes that arefit for their purpose. ■

Anthony G. Lee is in the School of BiologicalSciences, University of Southampton,Southampton SO16 7PX, UK.e-mail: a.g.lee@soton.ac.co.uk

1. Gonen, T. et al. Nature 438, 633–638 (2005).2. Jost, P. C., Griffith, O. H., Capaldi, R. A. & Vanderkooi, G.

Proc. Natl Acad. Sci. USA 70, 480–484 (1973).3. Luecke, H., Schobert, B., Richter, H. T., Cartailler, J. P. &

Lanyi, J. K. J. Mol. Biol. 291, 899–911 (1999). 4. Gonen, T., Sliz, P., Kistler, J., Cheng, Y. & Walz, T. Nature

429, 193–197 (2004). 5. Zampighi, G., Simon, S. A., Robertson, J. D., McIntosh, T. J.

& Costello, M. J. J. Cell Biol. 93, 175–189 (1982). 6. Pascher, I., Lundmark, M., Nyholm, P. G. & Sundell, J.

Biochim. Biophys. Acta 1113, 339–373 (1992).7. Murata, T., Yamato, I., Kakinuma, Y., Leslie, A. G. W. &

Walker, J. E. Science 308, 654–659 (2005).8. Lee, A. G. Biochim. Biophys. Acta 1612, 1–40 (2003).

liquid water. Recent discoveries include deltasand previously unknown channel systems,suggesting that abundant surface run-offoccurred in the distant past.

Indications of the previous existence ofwater on Mars have also come from a differentsource — data sent back by the Mars Explo-ration Rover Opportunity from the MeridianiPlanum landing site. Most notably, the discov-ery4 of haematite and sulphate minerals suchas jarosite on the surface at Meridiani suggeststhat liquid water must have been present at thesurface and as ground water at some stage.

On Earth, the reaction of water, especiallyhot water, with rock leads to the formation ofwater-bearing alteration products, includingclays. So clay minerals should be abundant onMars, especially early in the planet’s historywhen water was present and there was heatfrom volcanoes and large impact craters5–8. Onthe basis of earlier spectra, a few voices haveindeed argued that hydrated silicate clay min-erals are present9,10. The consensus, however,also taking into account the recent data fromthe Mars Exploration Rovers, has been that themineralogy of the martian surface is charac-terized by acid-sulphate processes.

Compared with Earth, where a wide rangeof minerals is formed by aqueous action, thisacid-sulphate environment limits the numberof minerals that can be created. In particular,clays are not usually produced in such envi-ronments11,12. It also seems that these acid-sulphate conditions have been prevalent formuch of Mars’ history, in that there is a lack of

PLANETARY SCIENCE

Clays in the history of MarsHorton Newsom

The stream of revelations from Mars continues. The latest news — thediscovery of clays in ancient terrains — helps to fill in the picture of the past existence of liquid water on the planet’s surface.

Thanks to three orbiting spacecraft and tworovers that continue to return data, we nowhave a great deal of evidence that abundantsurface water once existed on Mars. But untilnow something has been missing. Waterwould be expected to alter the surface miner-als to form clays, yet that hallmark of aqueousaction seemed to be absent.

The mystery has been solved by new resultsfrom the OMEGA near-infrared spectrometerexperiment on the Mars Express spacecraft.Clays do indeed exist on Mars, but only in particular places. The OMEGA instrument’sinitial discovery1 of clays on ancient martiansurfaces, published earlier this year, is now fol-lowed by the more comprehensive account byPoulet et al. that appears on page 623 of thisissue2. Clays are a subgroup of the phyllo-silicates, water-bearing silicate minerals withlayered structures, and Poulet and colleagues’observations show that different types of phyllosilicates are present in some outcrops ofthe ancient highlands of Mars. In addition to clearing up the mystery of the missing clay, this observation provides evidence for adrastic change in the chemistry of surfaceprocesses early in martian history.

Apart from circumstantial evidence for therole of water in forming gulleys at high lati-tudes3, there are no other indications of largeamounts of liquid water at the surface of Marstoday. By contrast, there has been plenty of evi-dence for abundant past water on Mars, pro-vided by images of geomorphic features thatseem to have been produced by the action of

Sulphur-rich soil

Dep

th b

elow

sur

face

Later Mars surface:acid-sulphate alteration due to increasing amounts of sulphur-rich soil

Early Mars surface: phyllosilicate alteration

Recent meteorites

Ancient meteorites

Subsurface: alkaline water chemistry dominated by igneous mineral/water reactions

4.6 4.0 3.0 2.0 1.0 0

Age (billions of years)

Figure 1 | Water–rock interactionon Mars. The data from Poulet etal.2 suggest that phyllosilicates,water-bearing silicate minerals thatinclude clays, may have formedearly in Mars’ history. The surfacelater became acidic, leading to theformation of sulphate-rich aqueous-alteration minerals. Martianmeteorites that have reached Earthwere ejected by impacts and arederived from below the planet’ssurface. The alteration phases inmeteorites of both ancient andrecent origin generally showevidence for modification in a morealkaline aqueous environment16.Presumably, then, the sulphur-richacidic material that hasaccumulated on the surface is notpresent at depth.

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