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

J. Biol. Chem., Vol. 280, Issue 12, 11043-11051, March 25, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/12/11043    most recent M412472200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jensen, P. H. Articles by Højrup, P. Search for Related Content PubMed PubMed Citation Articles by Jensen, P. H. Articles by Højrup, P. Social Bookmarking                      What's this?

Characterization of the Oligomer Structure of Recombinant Human Mannan-binding Lectin^*

Pia H. Jensen, Dietmar Weilguny, Finn Matthiesen, Kirsten A. McGuire, Lei Shi¶, and Peter Højrup||

From the Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, NatImmune A/S, Fruebjergvej 3, Box 3, DK-2100 Copenhagen, Denmark, and ^¶Laboratory of Developmental Immunology, GRJ1402, MassGeneral Hospital for Children, Harvard Medical School, Boston, Massachusetts 02114

Mannan-binding lectin (MBL) belongs to a family of proteins called the collectins, which show large differences in their ultrastructures. These differences are believed to be determined by different N-terminal disulfide-bonding patterns. So far only the bonding pattern of two of the simple forms (recombinant rat MBL-C and bovine CL-43) have been determined. Recombinant MBL expressed in human cells was purified, and the structure of the N-terminal region was determined. Preliminary results on human plasma-derived MBL revealed high similarity to the recombinant protein. Here we report the structure of the N-terminal part of recombinant human MBL and present a model to explain the oligomerization pattern. Using a strategy of consecutive enzymatic digestions and matrix-assisted laser desorption ionization mass spectrometry, we succeeded in identifying a number of disulfide-linked peptides from the N-terminal cysteine-rich region. Based on these building blocks, we propose a model that can explain the various oligomeric forms found in purified MBL preparations. Furthermore, the model was challenged by the production of cysteine to serine mutants of the three N-terminally situated cysteines. The oligomerization patterns of these mutants support the proposed model. The model indicates that the polypeptide dimer is the basic unit in the oligomerization.

Received for publication, November 4, 2004 , and in revised form, January 14, 2005.

^* This work was supported by NatImmune A/S, the Danish Ministry of Science, Technology, and Innovation, and the Novo Nordisk Foundation. The molecular electron microscopy facility at Harvard Medical School was established by a generous donation from the Giovanni Armenise Harvard Center for Structural Biology and is maintained by funds from National Institutes of Health Grant GM62580. 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.

^|| To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark. Tel.: 45-65502371; Fax: 45-65502467; E-mail: php{at}bmb.sdu.dk.

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

This article has been cited by other articles:

				J. C. Panepinto, K. W. Komperda, M. Hacham, S. Shin, X. Liu, and P. R. Williamson Binding of Serum Mannan Binding Lectin to a Cell Integrity-Defective Cryptococcus neoformans ccr4{Delta} Mutant Infect. Immun., October 1, 2007; 75(10): 4769 - 4779. [Abstract] [Full Text] [PDF]

				F. Teillet, M. Lacroix, S. Thiel, D. Weilguny, T. Agger, G. J. Arlaud, and N. M. Thielens Identification of the Site of Human Mannan-Binding Lectin Involved in the Interaction with Its Partner Serine Proteases: The Essential Role of Lys55 J. Immunol., May 1, 2007; 178(9): 5710 - 5716. [Abstract] [Full Text] [PDF]

				M. Dong, S. Xu, C. L. P. Oliveira, J. S. Pedersen, S. Thiel, F. Besenbacher, and T. Vorup-Jensen Conformational Changes in Mannan-Binding Lectin Bound to Ligand Surfaces J. Immunol., March 1, 2007; 178(5): 3016 - 3022. [Abstract] [Full Text] [PDF]