Blog
About

1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Clip-Segment of the von Willebrand Domain 1 of the BMP Modulator Protein Crossveinless 2 Is Preformed

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Bone Morphogenetic Proteins (BMPs) are secreted protein hormones that act as morphogens and exert essential roles during embryonic development of tissues and organs. Signaling by BMPs occurs via hetero-oligomerization of two types of serine/threonine kinase transmembrane receptors. Due to the small number of available receptors for a large number of BMP ligands ligand-receptor promiscuity presents an evident problem requiring additional regulatory mechanisms for ligand-specific signaling. Such additional regulation is achieved through a plethora of extracellular antagonists, among them members of the Chordin superfamily, that modulate BMP signaling activity by binding. The key-element in Chordin-related antagonists for interacting with BMPs is the von Willebrand type C (VWC) module, which is a small domain of about 50 to 60 residues occurring in many different proteins. Although a structure of the VWC domain of the Chordin-member Crossveinless 2 (CV2) bound to BMP-2 has been determined by X-ray crystallography, the molecular mechanism by which the VWC domain binds BMPs has remained unclear. Here we present the NMR structure of the Danio rerio CV2 VWC1 domain in its unbound state showing that the key features for high affinity binding to BMP-2 is a pre-oriented peptide loop.

          Related collections

          Most cited references 46

          • Record: found
          • Abstract: found
          • Article: not found

          SMART, a simple modular architecture research tool: identification of signaling domains.

          Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            How cells read TGF-beta signals.

             J Massagué (2000)
            Cell proliferation, differentiation and death are controlled by a multitude of cell-cell signals, and loss of this control has devastating consequences. Prominent among these regulatory signals is the transforming growth factor-beta (TGF-beta) family of cytokines, which can trigger a bewildering diversity of responses, depending on the genetic makeup and environment of the target cell. What are the networks of cell-specific molecules that mould the TGF-beta response to each cell's needs?
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk.

              Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGF-beta) superfamily, bind to two different serine/threonine kinase receptors, and mediate their signals through Smad-dependent and Smad-independent pathways. Receptor regulated-Smad (R-Smad) proteins specific for the BMP pathways interact with various proteins, including transcription factor Runx, and transmit specific signals in target cells. The recent development of DNA microarray techniques has allowed us to identify many BMP target genes. BMP signaling is modulated by various molecules, including inhibitory Smads (I-Smads). Moreover, recent findings have revealed that BMP pathways interact with other signaling pathways, and such signaling cross-talk plays pivotal roles in growth and differentiation of target cells.
                Bookmark

                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                25 September 2013
                October 2013
                : 18
                : 10
                : 11658-11682
                Affiliations
                [1 ]Julius-von-Sachs Institut für Biowissenschaften der Universität Würzburg, Julius-von-Sachs Platz 2, Würzburg D-97082, Germany; E-Mails: juliane.fiebig@ 123456botanik.uni-wuerzburg.de (J.E.F.); stella.keiper@ 123456biozentrum.uni-wuerzburg.de (S.E.W.); ma.bauer@ 123456botanik.uni-wuerzburg.de (M.B.)
                [2 ]Lehrstuhl für Physiologische Chemie II, Biozentrum der Universität Würzburg, Am Hubland, Würzburg D-97074, Germany; E-Mails: liyanqiu@ 123456biozentrum.uni-wuerzburg.de (L.-Y.Q.); jinli.zhang@ 123456mso.umt.edu (J.-L.Z.); sebald@ 123456biozentrum.uni-wuerzburg.de (W.S.)
                [3 ]Leibnizinstitut für Molekulare Pharmakologie (FMP), Campus Berlin-Buch, Robert-Roessle Str. 10, Berlin D-13125, Germany; E-Mails: schmieder@ 123456fmp-berlin.de (P.S.); beerbaum@ 123456fmp-berlin.de (M.B.); oschkinat@ 123456fmp-berlin.de (H.O.)
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: mueller@ 123456biozentrum.uni-wuerzburg.de ; Tel.: +49-931-318-9207; Fax: +49-931-318-6158.
                Article
                molecules-18-11658
                10.3390/molecules181011658
                6270503
                24071977
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                Categories
                Article

                Comments

                Comment on this article