HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 32, 23219-23230, August 10, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/32/23219    most recent M702514200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leppänen, V.-M. Articles by Pihlajamaa, T. Search for Related Content PubMed PubMed Citation Articles by Leppänen, V.-M. Articles by Pihlajamaa, T. Social Bookmarking                      What's this?

Crystal Structure of the N-terminal NC4 Domain of Collagen IX, a Zinc Binding Member of the Laminin-Neurexin-Sex Hormone Binding Globulin (LNS) Domain Family^*

Veli-Matti Leppänen, Helena Tossavainen, Perttu Permi, Lari Lehtiö, Gunilla Rönnholm, Adrian Goldman, Ilkka Kilpelaïnen, and Tero Pihlajamaa¹

From the Program in Structural Biology and Biophysics, Institute of Biotechnology and the Laboratory of Organic Chemistry, Department of Chemistry, University of Helsinki, FI-00014 Helsinki, Finland

Collagen IX, located on the surface of collagen fibrils, is crucial for cartilage integrity and stability. The N-terminal NC4 domain of the 1(IX) chain is probably important in this because it interacts with various macromolecules such as proteoglycans and cartilage oligomeric matrix protein. At least 17 distinct collagen polypeptides carry an NC4-like unit near their N terminus, but this report, describing the crystal structure of NC4 at 1.8-Å resolution, represents the first atomic level structure for these domains. The structure is similar to previously characterized laminin-neurexin-sex hormone binding globulin (LNS) structures, dominated by an antiparallel -sheet sandwich. In addition, a zinc ion was found in a position similar to that of the metal binding site of other LNS domains. A partial backbone NMR assignment of NC4 was obtained and utilized in NMR titration studies to investigate the zinc binding in solution state and to quantitate the affinity of metal binding. The K_d of 11.5 mM suggests a regulatory rather than a structural role for zinc in solution. NMR titration with a heparin tetrasaccharide revealed the presence of a secondary binding site for heparin on NC4, showing structural and functional conservation with thrombospondin-1, but a markedly reduced affinity for the ligand. Also the overall arrangement of the N and C termini of NC4 resembles most closely the N-terminal domain of thrombospondin-1, distinguishing the two from the majority of the published LNS structures.

Received for publication, March 23, 2007 , and in revised form, May 22, 2007.

^* This work was supported by Academy of Finland Grants 106411 (to T. P.), 1206228 (to I. K.), 70891 (to V.-M. L.), 1105157 and 1111771 (to A. G.), and 106852 (to P. P.) as well as by funding from the Sigrid Juselius Foundation and Biocentrum Helsinki (to A. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and structure factors (code 2UUR) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

¹ To whom correspondence should be addressed: NMR Laboratory, Inst. of Biotechnology, P. O. Box 65, University of Helsinki, FI-00014 Helsinki, Finland. Tel.: 358-9-19159544; Fax: 358-9-19159541; E-mail: Tero.Pihlajamaa{at}helsinki.fi.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Reissner, M. Klose, R. Fairless, and M. Missler Mutational analysis of the neurexin/neuroligin complex reveals essential and regulatory components PNAS, September 30, 2008; 105(39): 15124 - 15129. [Abstract] [Full Text] [PDF]