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.
a novel layered fold and its biological implication
Kemin Tan1,3,
Mark Duquette2,4,
Jin-huan Liu1,3,
Yicheng Dong1,3,
Rongguang Zhang7,
Andrzej Joachimiak7,
Jack Lawler2,4, and
Jia-huai Wang1,5,6
1 Dana-Farber Cancer Institute, Boston, MA 02115 2 Beth Israel Deaconess Medical Center, Boston, MA 02215 3 Departments of Medicine, Harvard Medical School, Boston, MA 02115 4 Pathology, Harvard Medical School, Boston, MA 02115 5 Pediatrics, Harvard Medical School, Boston, MA 02115 6 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 7 Biosciences Division, Argonne National Laboratories, Argonne, IL 60439
Address correspondence to Jia-huai Wang, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Room SM-1036, Boston, MA 02115. Tel.: (617) 632-3983. Fax: (617) 632-4393. E-mail: jwang{at}red.dfci.harvard.edu; or Jack Lawler, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Ave., Boston, MA 02215. Tel.: (617) 667-1694. Fax: (617) 667-3591. E-mail: lawler{at}mbcrr.harvard.edu
Abstract:
Thrombospondin-1 (TSP-1) contains three type 1 repeats (TSRs),which mediate cell attachment, glycosaminoglycan binding, inhibitionof angiogenesis, activation of TGFß, and inhibitionof matrix metalloproteinases. The crystal structure of the TSRsreported in this article reveals a novel, antiparallel, three-strandedfold that consists of alternating stacked layers of tryptophanand arginine residues from respective strands, capped by disulfidebonds on each end. The front face of the TSR contains a right-handedspiral, positively charged groove that might be the "recognition"face, mediating interactions with various ligands. This is thefirst high-resolution crystal structure of a TSR domain thatprovides a prototypic architecture for structural and functionalexploration of the diverse members of the TSR superfamily.
Key Words: thrombospondin; TSR domain; X-ray structure; angiogenesis; GAG binding
The editors suggest the following Related Resources on Science sites:
Shape change in the receptor for gliding motility in Plasmodium sporozoites.
G. Song, A. C. Koksal, C. Lu, and T. A. Springer (2012)
PNAS
109, 21420-21425
|Abstract »|Full Text »|PDF »
The RGD finger of Del-1 is a unique structural feature critical for integrin binding.
T. Schurpf, Q. Chen, J.-h. Liu, R. Wang, T. A. Springer, and J.-h. Wang (2012)
FASEB J
26, 3412-3420
|Abstract »|Full Text »|PDF »
Unexpected fold in the circumsporozoite protein target of malaria vaccines.
M. B. Doud, A. C. Koksal, L.-Z. Mi, G. Song, C. Lu, and T. A. Springer (2012)
PNAS
109, 7817-7822
|Abstract »|Full Text »|PDF »
Analysis of the Conformation and Function of the Plasmodium falciparum Merozoite Proteins MTRAP and PTRAMP.
O. Uchime, R. Herrera, K. Reiter, S. Kotova, R. L. Shimp Jr., K. Miura, D. Jones, J. Lebowitz, X. Ambroggio, D. E. Hurt, et al. (2012)
Eukaryot. Cell
11, 615-625
|Abstract »|Full Text »|PDF »
Molecular Basis for the Regulation of Angiogenesis by Thrombospondin-1 and -2.
P. R. Lawler and J. Lawler (2012)
Cold Spring Harb Perspect Med
2, a006627
|Abstract »|Full Text »|PDF »
Structure of Complement C6 Suggests a Mechanism for Initiation and Unidirectional, Sequential Assembly of Membrane Attack Complex (MAC).
A. E. Aleshin, I. U. Schraufstatter, B. Stec, L. A. Bankston, R. C. Liddington, and R. G. DiScipio (2012)
J. Biol. Chem.
287, 10210-10222
|Abstract »|Full Text »|PDF »
CD36 Ectodomain Phosphorylation Blocks Thrombospondin-1 Binding: Structure-Function Relationships and Regulation by Protein Kinase C.
L.-Y. Chu and R. L. Silverstein (2012)
Arterioscler Thromb Vasc Biol
32, 760-767
|Abstract »|Full Text »|PDF »
Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis.
B. C. Bernardo, D. Belluoccio, L. Rowley, C. B. Little, U. Hansen, and J. F. Bateman (2011)
J. Biol. Chem.
286, 37758-37767
|Abstract »|Full Text »|PDF »
The Thrombospondins.
J. C. Adams and J. Lawler (2011)
Cold Spring Harb Perspect Biol
3, a009712
|Abstract »|Full Text »|PDF »
First Structural Glimpse of CCN3 and CCN5 Multifunctional Signaling Regulators Elucidated by Small Angle X-ray Scattering.
K. P. Holbourn, M. Malfois, and K. R. Acharya (2011)
J. Biol. Chem.
286, 22243-22249
|Abstract »|Full Text »|PDF »
The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins.
M. F. Bolliger, D. C. Martinelli, and T. C. Sudhof (2011)
PNAS
108, 2534-2539
|Abstract »|Full Text »|PDF »
Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria.
S. Das, K. A. Owen, K. T. Ly, D. Park, S. G. Black, J. M. Wilson, C. D. Sifri, K. S. Ravichandran, P. B. Ernst, and J. E. Casanova (2011)
PNAS
108, 2136-2141
|Abstract »|Full Text »|PDF »
Thrombospondin-1 Inhibits VEGF Receptor-2 Signaling by Disrupting Its Association with CD47.
S. Kaur, G. Martin-Manso, M. L. Pendrak, S. H. Garfield, J. S. Isenberg, and D. D. Roberts (2010)
J. Biol. Chem.
285, 38923-38932
|Abstract »|Full Text »|PDF »
The Evolution of Thrombospondins and Their Ligand-Binding Activities.
ADAMTSL-6 Is a Novel Extracellular Matrix Protein That Binds to Fibrillin-1 and Promotes Fibrillin-1 Fibril Formation.
K. Tsutsui, R.-i. Manabe, T. Yamada, I. Nakano, Y. Oguri, D. R. Keene, G. Sengle, L. Y. Sakai, and K. Sekiguchi (2010)
J. Biol. Chem.
285, 4870-4882
|Abstract »|Full Text »|PDF »
Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor.
M. Akiyama, S. Takeda, K. Kokame, J. Takagi, and T. Miyata (2009)
PNAS
106, 19274-19279
|Abstract »|Full Text »|PDF »
Post-translational Modification of Thrombospondin Type-1 Repeats in ADAMTS-like 1/Punctin-1 by C-Mannosylation of Tryptophan.
L. W. Wang, C. Leonhard-Melief, R. S. Haltiwanger, and S. S. Apte (2009)
J. Biol. Chem.
284, 30004-30015
|Abstract »|Full Text »|PDF »
Interactions among Stalk Modules of Thrombospondin-1.
Structure of the Plasmodium falciparum Circumsporozoite Protein, a Leading Malaria Vaccine Candidate.
M. L. Plassmeyer, K. Reiter, R. L. Shimp Jr., S. Kotova, P. D. Smith, D. E. Hurt, B. House, X. Zou, Y. Zhang, M. Hickman, et al. (2009)
J. Biol. Chem.
284, 26951-26963
|Abstract »|Full Text »|PDF »
The first deletion mutation in the TSP1-6 repeat domain of ADAMTS13 in a family with inherited thrombotic thrombocytopenic purpura.
R. Palla, S. Lavoretano, R. Lombardi, I. Garagiola, M. Karimi, A. Afrasiabi, M. Ramzi, R. De Cristofaro, and F. Peyvandi (2009)
Haematologica
94, 289-293
|Abstract »|Full Text »|PDF »
The C. elegans F-spondin family protein SPON-1 maintains cell adhesion in neural and non-neural tissues.
W.-M. Woo, E. C. Berry, M. L. Hudson, R. E. Swale, A. Goncharov, and A. D. Chisholm (2008)
Development
135, 2747-2756
|Abstract »|Full Text »|PDF »
The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis.
C. Kemper, L. M. Mitchell, L. Zhang, and D. E. Hourcade (2008)
PNAS
105, 9023-9028
|Abstract »|Full Text »|PDF »
Extracellular matrix retention of thrombospondin 1 is controlled by its conserved C-terminal region.
J. C. Adams, A. A. Bentley, M. Kvansakul, D. Hatherley, and E. Hohenester (2008)
J. Cell Sci.
121, 784-795
|Abstract »|Full Text »|PDF »
Proteolysis and membrane capture of F-spondin generates combinatorial guidance cues from a single molecule.
S. Zisman, K. Marom, O. Avraham, L. Rinsky-Halivni, U. Gai, G. Kligun, V. Tzarfaty-Majar, T. Suzuki, and A. Klar (2007)
J. Cell Biol.
178, 1237-1249
|Abstract »|Full Text »|PDF »
Immunochemical Analysis of the Structure of the Signature Domains of Thrombospondin-1 and Thrombospondin-2 in Low Calcium Concentrations.
D. S. Annis, K. A. Gunderson, and D. F. Mosher (2007)
J. Biol. Chem.
282, 27067-27075
|Abstract »|Full Text »|PDF »
NetCGlyc 1.0: prediction of mammalian C-mannosylation sites.
TIMP-3 Inhibition of ADAMTS-4 (Aggrecanase-1) Is Modulated by Interactions between Aggrecan and the C-terminal Domain of ADAMTS-4.
G. J. Wayne, S.-J. Deng, A. Amour, S. Borman, R. Matico, H. L. Carter, and G. Murphy (2007)
J. Biol. Chem.
282, 20991-20998
|Abstract »|Full Text »|PDF »
Exosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloprotease.
W. Gao, P. J. Anderson, E. M. Majerus, E. A. Tuley, and J. E. Sadler (2006)
PNAS
103, 19099-19104
|Abstract »|Full Text »|PDF »
Identification and Characterization of abeta1,3-Glucosyltransferase That Synthesizes the Glc-beta1,3-Fuc Disaccharide on Thrombospondin Type 1 Repeats.
K. Kozma, J. J. Keusch, B. Hegemann, K. B. Luther, D. Klein, D. Hess, R. S. Haltiwanger, and J. Hofsteenge (2006)
J. Biol. Chem.
281, 36742-36751
|Abstract »|Full Text »|PDF »
CD47 Is Necessary for Inhibition of Nitric Oxide-stimulated Vascular Cell Responses by Thrombospondin-1.
J. S. Isenberg, L. A. Ridnour, J. Dimitry, W. A. Frazier, D. A. Wink, and D. D. Roberts (2006)
J. Biol. Chem.
281, 26069-26080
|Abstract »|Full Text »|PDF »
ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2.
A. X. Torres-Collado, W. Kisiel, M. L. Iruela-Arispe, and J. C. Rodriguez-Manzaneque (2006)
J. Biol. Chem.
281, 17827-17837
|Abstract »|Full Text »|PDF »
A Conserved Molecular Motor Drives Cell Invasion and Gliding Motility across Malaria Life Cycle Stages and Other Apicomplexan Parasites.
J. Baum, D. Richard, J. Healer, M. Rug, Z. Krnajski, T.-W. Gilberger, J. L. Green, A. A. Holder, and A. F. Cowman (2006)
J. Biol. Chem.
281, 5197-5208
|Abstract »|Full Text »|PDF »
Antiangiogenic Treatment with Three Thrombospondin-1 Type 1 Repeats versus Gemcitabine in an Orthotopic Human Pancreatic Cancer Model.
X. Zhang, E. Galardi, M. Duquette, J. Lawler, and S. Parangi (2005)
Clin. Cancer Res.
11, 5622-5630
|Abstract »|Full Text »|PDF »
Increased expression of protein C-mannosylation in the aortic vessels of diabetic Zucker rats.
Y. Ihara, S. Manabe, M. Kanda, H. Kawano, T. Nakayama, I. Sekine, T. Kondo, and Y. Ito (2005)
Glycobiology
15, 383-392
|Abstract »|Full Text »|PDF »
Antiangiogenic Treatment with the Three Thrombospondin-1 Type 1 Repeats Recombinant Protein in an Orthotopic Human Pancreatic Cancer Model.
X. Zhang, E. Galardi, M. Duquette, M. Delic, J. Lawler, and S. Parangi (2005)
Clin. Cancer Res.
11, 2337-2344
|Abstract »|Full Text »|PDF »
Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is mediated by {beta}1 integrins.
S. M. Short, A. Derrien, R. P. Narsimhan, J. Lawler, D. E. Ingber, and B. R. Zetter (2005)
J. Cell Biol.
168, 643-653
|Abstract »|Full Text »|PDF »
Structural Basis for the Functions of Endogenous Angiogenesis Inhibitors.
M.A. GRANT and R. KALLUR (2005)
Cold Spring Harb Symp Quant Biol
70, 399-417
|Abstract »|PDF »
The Tryptophan-rich Motifs of the Thrombospondin Type 1 Repeats Bind VLAL Motifs in the Latent Transforming Growth Factor-{beta} Complex.
G. D. Young and J. E. Murphy-Ullrich (2004)
J. Biol. Chem.
279, 47633-47642
|Abstract »|Full Text »|PDF »
Targeted Mutagenesis of the Angiogenic Protein CCN1 (CYR61): SELECTIVE INACTIVATION OF INTEGRIN {alpha}6{beta}1-HEPARAN SULFATE PROTEOGLYCAN CORECEPTOR-MEDIATED CELLULAR FUNCTIONS.
S.-J. Leu, N. Chen, C.-C. Chen, V. Todorovic, T. Bai, V. Juric, Y. Liu, G. Yan, S. C.-T. Lam, and L. F. Lau (2004)
J. Biol. Chem.
279, 44177-44187
|Abstract »|Full Text »|PDF »
Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome.
M. Matsumoto, K. Kokame, K. Soejima, M. Miura, S. Hayashi, Y. Fujii, A. Iwai, E. Ito, Y. Tsuji, M. Takeda-Shitaka, et al. (2004)
Blood
103, 1305-1310
|Abstract »|Full Text »|PDF »
Design of a Partial Peptide Mimetic of Anginex with Antiangiogenic and Anticancer Activity.
K. H. Mayo, R. P. M. Dings, C. Flader, I. Nesmelova, B. Hargittai, D. W. J. van der Schaft, L. I. van Eijk, D. Walek, J. Haseman, T. R. Hoye, et al. (2003)
J. Biol. Chem.
278, 45746-45752
|Abstract »|Full Text »|PDF »
The species-specific egg receptor for sea urchin sperm adhesion is EBR1,a novel ADAMTS protein.
