Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 1 November 1996:
Vol. 274. no. 5288, pp. 761 - 765
DOI: 10.1126/science.274.5288.761
Prev | Table of Contents | Next

Reports

The Crystal Structure of a Five-Stranded Coiled Coil in COMP: A Prototype Ion Channel?

Vladimir N. Malashkevich, * Richard A. Kammerer, Vladimir P. Efimov, dagger Therese Schulthess, Jürgen Engel

Oligomerization by the formation of alpha -helical bundles is common in many proteins. The crystal structure of a parallel pentameric coiled coil, constituting the oligomerization domain in the cartilage oligomeric matrix protein (COMP), was determined at 2.05 angstroms resolution. The same structure probably occurs in two other extracellular matrix proteins, thrombospondins 3 and 4. Complementary hydrophobic interactions and conserved disulfide bridges between the alpha  helices result in a thermostable structure with unusual properties. The long hydrophobic axial pore is filled with water molecules but can also accommodate small apolar groups. An "ion trap" is formed inside the pore by a ring of conserved glutamines, which binds chloride and probably other monatomic anions. The oligomerization domain of COMP has marked similarities with proposed models of the pentameric transmembrane ion channels in phospholamban and the acetylcholine receptor.

V. N. Malashkevich, Department of Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
R. A. Kammerer, V. P. Efimov, T. Schulthess, J. Engel, Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
*   To whom correspondence should be addressed.

dagger    Present address: Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA.

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Epidermal Growth Factor-like Repeats of Thrombospondins Activate Phospholipase C{gamma} and Increase Epithelial Cell Migration through Indirect Epidermal Growth Factor Receptor Activation.
A. Liu, P. Garg, S. Yang, P. Gong, M. A. Pallero, D. S. Annis, Y. Liu, A. Passaniti, D. Mann, D. F. Mosher, et al. (2009)
J. Biol. Chem. 284, 6389-6402
   Abstract »    Full Text »    PDF »
Cartilage Oligomeric Matrix Protein Protects Cells against Death by Elevating Members of the IAP Family of Survival Proteins.
V. Gagarina, A. L. Carlberg, L. Pereira-Mouries, and D. J. Hall (2008)
J. Biol. Chem. 283, 648-659
   Abstract »    Full Text »    PDF »
The structure of phospholamban pentamer reveals a channel-like architecture in membranes.
K. Oxenoid and J. J. Chou (2005)
PNAS 102, 10870-10875
   Abstract »    Full Text »    PDF »
Mice with a Disruption of the Thrombospondin 3 Gene Differ in Geometric and Biomechanical Properties of Bone and Have Accelerated Development of the Femoral Head.
K. D. Hankenson, S. G. Hormuzdi, J. A. Meganck, and P. Bornstein (2005)
Mol. Cell. Biol. 25, 5599-5606
   Abstract »    Full Text »    PDF »
Roles of the N-terminal Domain on the Function and Quaternary Structure of the Ionotropic Glutamate Receptor.
S. Matsuda, Y. Kamiya, and M. Yuzaki (2005)
J. Biol. Chem. 280, 20021-20029
   Abstract »    Full Text »    PDF »
Secretion of Cartilage Oligomeric Matrix Protein Is Affected by the Signal Peptide.
P. Holden, D. R. Keene, G. P. Lunstrum, H. P. Bachinger, and W. A. Horton (2005)
J. Biol. Chem. 280, 17172-17179
   Abstract »    Full Text »    PDF »
Atomic structure of a tryptophan-zipper pentamer.
J. Liu, W. Yong, Y. Deng, N. R. Kallenbach, and M. Lu (2004)
PNAS 101, 16156-16161
   Abstract »    Full Text »    PDF »
From The Cover: De novo design of defined helical bundles in membrane environments.
B. Bilgicer and K. Kumar (2004)
PNAS 101, 15324-15329
   Abstract »    Full Text »    PDF »
COMP-Ang1: A designed angiopoietin-1 variant with nonleaky angiogenic activity.
C.-H. Cho, R. A. Kammerer, H. J. Lee, M. O. Steinmetz, Y. S. Ryu, S. H. Lee, K. Yasunaga, K.-T. Kim, I. Kim, H.-H. Choi, et al. (2004)
PNAS 101, 5547-5552
   Abstract »    Full Text »    PDF »
Shift of fibril-forming ability of the designed {alpha}-helical coiled-coil peptides into the physiological pH region.
T.N. Melnik, V. Villard, V. Vasiliev, G. Corradin, A.V. Kajava, and S.A. Potekhin (2003)
Protein Eng. Des. Sel. 16, 1125-1130
   Abstract »    Full Text »    PDF »
Oligomerization, Membrane Anchoring, and Cellulose-binding Characteristics of AbpS, a Receptor-like Streptomyces Protein.
S. Walter and H. Schrempf (2003)
J. Biol. Chem. 278, 26639-26647
   Abstract »    Full Text »    PDF »
On the Conformation of the COOH-terminal Domain of the Large Mechanosensitive Channel MscL.
A. Anishkin, V. Gendel, N. A. Sharifi, C.-S. Chiang, L. Shirinian, H. R. Guy, and S. Sukharev (2003)
J. Gen. Physiol. 121, 227-244
   Abstract »    Full Text »    PDF »
Trimers of the fibronectin cell adhesion domain localize to actin filament bundles and undergo rearward translocation.
F. Coussen, D. Choquet, M. P. Sheetz, and H. P. Erickson (2002)
J. Cell Sci. 115, 2581-2590
   Abstract »    Full Text »    PDF »
Analysis of Heterophilic and Homophilic Interactions of Cadherins Using the c-Jun/c-Fos Dimerization Domains.
T. Ahrens, O. Pertz, D. Haussinger, C. Fauser, T. Schulthess, and J. Engel (2002)
J. Biol. Chem. 277, 19455-19460
   Abstract »    Full Text »    PDF »
C-Terminal Interaction Is Essential for Surface Trafficking But Not for Heteromeric Assembly of GABAB Receptors.
A. Pagano, G. Rovelli, J. Mosbacher, T. Lohmann, B. Duthey, D. Stauffer, D. Ristig, V. Schuler, I. Meigel, C. Lampert, et al. (2001)
J. Neurosci. 21, 1189-1202
   Abstract »    Full Text »    PDF »
A Cartilage Oligomeric Matrix Protein Mutation Associated with Pseudoachondroplasia Changes the Structural and Functional Properties of the Type 3 Domain.
B. K. Maddox, A. Mokashi, D. R. Keene, and H. P. Bachinger (2000)
J. Biol. Chem. 275, 11412-11417
   Abstract »    Full Text »    PDF »
Cardiac-specific Overexpression of a Superinhibitory Pentameric Phospholamban Mutant Enhances Inhibition of Cardiac Function in Vivo.
J. Zhai, A. G. Schmidt, B. D. Hoit, Y. Kimura, D. H. MacLennan, and E. G. Kranias (2000)
J. Biol. Chem. 275, 10538-10544
   Abstract »    Full Text »    PDF »
Self-association and Domains of Interactions of an Amphipathic Helix Peptide Inhibitor of HIV-1 Integrase Assessed by Analytical Ultracentrifugation and NMR Experiments in Trifluoroethanol/H2O Mixtures.
R. G. Maroun, D. Krebs, S. El Antri, A. Deroussent, E. Lescot, F. Troalen, H. Porumb, M. E. Goldberg, and S. Fermandjian (1999)
J. Biol. Chem. 274, 34174-34185
   Abstract »    Full Text »    PDF »
A DNA pentaplex incorporating nucleobase quintets.
J. C. Chaput and C. Switzer (1999)
PNAS 96, 10614-10619
   Abstract »    Full Text »    PDF »
Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-A resolution.
V. N. Malashkevich, B. J. Schneider, M. L. McNally, M. A. Milhollen, J. X. Pang, and P. S. Kim (1999)
PNAS 96, 2662-2667
   Abstract »    Full Text »    PDF »
The Open Reading Frame III Product of Cauliflower Mosaic Virus Forms a Tetramer through a N-terminal Coiled-coil.
D. Leclerc, L. Burri, A. V. Kajava, J.-L. Mougeot, D. Hess, A. Lustig, G. Kleemann, and T. Hohn (1998)
J. Biol. Chem. 273, 29015-29021
   Abstract »    Full Text »    PDF »
A Far Upstream, Cell Type-specific Enhancer of the Mouse Thrombospondin 3 Gene Is Located within Intron 6 of the Adjacent Metaxin Gene.
M. Collins, P. Rojnuckarin, Y.-H. Zhu, and P. Bornstein (1998)
J. Biol. Chem. 273, 21816-21824
   Abstract »    Full Text »    PDF »
Cartilage Oligomeric Matrix Protein Shows High Affinity Zinc-dependent Interaction with Triple Helical Collagen.
K. Rosenberg, H. Olsson, M. Morgelin, and D. Heinegard (1998)
J. Biol. Chem. 273, 20397-20403
   Abstract »    Full Text »    PDF »
Helical Superstructures from Charged Poly(styrene)-Poly(isocyanodipeptide) Block Copolymers.
J. J. Cornelissen, M. Fischer, N. A. Sommerdijk, and R. J. Nolte (1998)
Science 280, 1427-1430
   Abstract »    Full Text »
A Single Cysteine, Cys-64, Is Essential for Assembly of Tenascin-C Hexabrachions.
J. A. Luczak, S. D. Redick, and J. E. Schwarzbauer (1998)
J. Biol. Chem. 273, 2073-2077
   Abstract »    Full Text »    PDF »
The Fate of Cartilage Oligomeric Matrix Protein Is Determined by the Cell Type in the Case of a Novel Mutation in Pseudoachondroplasia.
B. K. Maddox, D. R. Keene, L. Y. Sakai, N. L. Charbonneau, N. P. Morris, C. C. Ridgway, B. A. Boswell, M. D. Sussman, W. A. Horton, H. P. Bachinger, et al. (1997)
J. Biol. Chem. 272, 30993-30997
   Abstract »    Full Text »    PDF »
Post-translational Modifications in Cartilage Oligomeric Matrix Protein. CHARACTERIZATION OF THE N-LINKED OLIGOSACCHARIDES BY MATRIX-ASSISTED LASER DESORPTION IONIZATION TIME-OF-FLIGHT MASS SPECTROMETRY.
J. Zaia, R. E. Boynton, A. McIntosh, D. R. Marshak, H. Olsson, D. Heinegard, and F. P. Barry (1997)
J. Biol. Chem. 272, 14120-14126
   Abstract »    Full Text »    PDF »
Physical Characterization of the Procollagen Module of Human Thrombospondin 1 Expressed in Insect Cells.
T. M. Misenheimer, K. G. Huwiler, D. S. Annis, and D. F. Mosher (2000)
J. Biol. Chem. 275, 40938-40945
   Abstract »    Full Text »    PDF »
Mutations in Cartilage Oligomeric Matrix Protein Causing Pseudoachondroplasia and Multiple Epiphyseal Dysplasia Affect Binding of Calcium and Collagen I, II, and IX.
J. Thur, K. Rosenberg, D. P. Nitsche, T. Pihlajamaa, L. Ala-Kokko, D. Heinegard, M. Paulsson, and P. Maurer (2001)
J. Biol. Chem. 276, 6083-6092
   Abstract »    Full Text »    PDF »
Molecular Mass, Stoichiometry, and Assembly of 20 S Particles.
C. Wimmer, T. M. Hohl, C. A. Hughes, S. A. Muller, T. H. Sollner, A. Engel, and J. E. Rothman (2001)
J. Biol. Chem. 276, 29091-29097
   Abstract »    Full Text »    PDF »
Cartilage Oligomeric Matrix Protein Is a Calcium-binding Protein, and a Mutation in Its Type 3 Repeats Causes Conformational Changes.
H. Chen, M. Deere, J. T. Hecht, and J. Lawler (2000)
J. Biol. Chem. 275, 26538-26544
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)