Surface topographies at subnanometer-resolution reveal asymmetry and sidedness of aquaporin-1

Thomas Walz, Peter Tittmann, Karl H. Fuchs, Daniel J. Müller, Barbara L. Smith, Peter Agre, Heinz Gross, Andreas Engel

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Aquaporin-1 (AQP1) is an abundant protein in human erythrocyte membranes which functions as a specific and constitutively active water conducting pore. Solubilized and isolated as tetramer, it forms well-ordered two-dimensional (2D) crystals when reconstituted in the presence of lipids. Several high resolution projection maps of AQP1 have been determined, but information on its three-dimensional (3D) mass distribution is sparse. Here, we present surface reliefs at 0.9 nm resolution that were calculated from freeze-dried unidirectionally metal-shadowed AQP1 crystals as well as surface topographs recorded with the atomic force microscope of native crystals in buffer solution. Our results confirm the 3D map of negatively stained AQP1 crystals, which exhibited tetramers with four major protrusions on one side and a large central cavity on the other side of the membrane. Digestion of AQP1 crystals with carboxypeptidase Y, which cleaves off a 5 kDa intracellular C-terminal fragment, led to a reduction of the major protrusions, suggesting that the central cavity of the tetramer faces the outside of the cell. To interpret the results, sequence based structure predictions served as a guide.

Original languageEnglish (US)
Pages (from-to)907-918
Number of pages12
JournalJournal of molecular biology
Issue number5
StatePublished - Dec 20 1996


  • Aquaporin-1
  • Atomic force microscopy
  • Electron microscopy
  • Surface identification
  • Surface topography

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology


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