but cannot serve as a channel since the protein does not possess any trans-
membrane domains. The sequence of this protein is homologous to the large
extracellular N-terminal domain of the receptor that binds acetylcholine.
The structure of the acetylcholine-binding protein shows that the single
polypeptide chain is arranged in the same 5-fold symmetric arrangement,
evident from the electron microscopy studies of the receptor. This structure
provides the opportunity to investigate the mechanism of allosteric trans-
itions that mediate activation and desensitization of the receptor as research
groups continue their efforts to determine the structure of the receptor.402 PART 3 UNDERSTANDING BIOLOGICAL SYSTEMS USING PHYSICAL CHEMISTRY
References and further reading
Abramson, J., Smirnova, I., Kasho, V. et al. (2003)
Structure and mechanism of the lactose permease
of Escherichia coli. Science 301 , 610 –15.
Agee, P. and Kozono, D. (2003) Aquaporin water
channels: molecular mechanisms for human dis-
ease.FEBS Letters 555 , 72– 8.
Bass, R.B., Strop, P., Barclay, M., and Rees, D.C.
(2002) Crystal structure of Escherichia coliMscS, a
voltage-modulated and mechanosensitive channel.
Science 298 , 1582–7.
Brejc, K., van Dijk, W.J., Klaassen, R.V. et al.(2001)
Crystal structure of an ACh-binding protein
reveals the ligand-binding domain of nicotinic
receptors. Nature 411 , 269 –76.
Gouaux, E. and MacKinnon, R. (2005) Principles
of selective ion transport in channels and pumps.
Science 310 , 1461–5.
Grutter, T. and Changeux, J.P. (2001) Nicotinic
receptors in wonderland. Trends in Biochemical
Sciences 26 , 459 – 63.
Huang, Y., Lemieux, M.J., Song, J., Auer, M., and
Wang, D.N. (2003) Structure and mechanism
of the glycerol-3-phosphate transporter from
Escherichia coli. Science 301 , 616 –20.
Hunte, C., Screpanti, E., Venturi, M. et al. (2005)
Structure of a Na+/H+ antiporter and insights
into mechanism of action and regulation by pH.
Nature 435 , 1197–1201.
Karlin, A. (2002) Emerging structure of the nicotinic
acetylcholine receptor. Nature Re 9 iews Neuroscience
3 , 102–14.
Locher, K.P., Bass, R.B., and Rees, D.C. (2003)
Breaching the barrier. Science 301 , 603 – 4.
Long, S.B., Campbell, E.B., and MacKinnon, R.
(2005) Crystal structure of a mammalian voltage-
dependent Shaker family K+channel. Science 309 ,
897–903.
MacKinnon, R. (2003) Potassium channels. FEBS
Letters 55 , 62–5.
Miller, C. (2001) See potassium run. Nature 414 ,
23 – 4.
Miller, C. (2006) CLC chloride channels viewed
through a transporter lens. Nature 440 , 484 –9.
Miyazawa, A., Fujiyoshi, Y., Stowell, M., and
Unwin, N. (1999) Nicotinic acetylcholine receptor
at 4.6 Å resolution: transverse tunnels in the
channel wall.Journal of Molecular Biology 288 ,
765 – 86.
Roux, B., Allen, T., Berneche, S., and Im, W. (2004)
Theoretical and computational models of biolog-
ical ion channels. Quarterly Re 9 iews of Biophysics 37 ,
15 –103.
Shi, N., Ye, S., Alam, A., Chen, L., and Jiang, Y.
(2006) Atomic structure of a Na+and K+conduct-
ing channel. Nature 440 , 570 – 4.
Stroud, R.M., Savage, D., Mierke, L.J.W. et al. (2003)
Selectivity and conductance among the glycerol and
water conducting aquaporin family of channels.
FEBS Letters 555 , 79 – 84.
Unwin, N. (1993) Nicotinic acetylcholine receptor
at 9 Å resolution. Journal of Molecular Biology 229 ,
1101–24.
Yamashita, A., Singh, S.K., Kawate, T., Jin, Y., and
Gouaux, E. (2005) Crystal structure of a bacterial
homologue of Na+/Cl−dependent neurotransmitter
transporters. Nature 437 , 215 –23.
Yernool, D., Boudker, O., Jin, Y., and Gouaux, E.
(2004) Structure of a glutamate transporter
homologue from Pyrococcus horoikoshii. Nature 431 ,
811–18.