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

J. Biol. Chem., Vol. 282, Issue 15, 11573-11581, April 13, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/15/11573    most recent M610657200v1 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 Harrison, D. Articles by Hohenester, E. Search for Related Content PubMed PubMed Citation Articles by Harrison, D. Articles by Hohenester, E. Social Bookmarking                      What's this?

Crystal Structure and Cell Surface Anchorage Sites of Laminin 1LG4-5^*

David Harrison¹, Sadaf-Ahmahni Hussain¹, Ariana C. Combs^¶, James M. Ervasti^¶, Peter D. Yurchenco, and Erhard Hohenester²

From the Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the ^¶Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, and the Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom

The laminin G-like (LG) domains of laminin-111, a glycoprotein widely expressed during embryogenesis, provide cell anchoring and receptor binding sites that are involved in basement membrane assembly and cell signaling. We now report the crystal structure of the laminin 1LG4-5 domains and provide a mutational analysis of heparin, -dystroglycan, and galactosylsulfatide binding. The two domains of 1LG4-5 are arranged in a V-shaped fashion similar to that observed with laminin 2 LG4-5 but with a substantially different interdomain angle. Recombinant 1LG4-5 binding to heparin, -dystroglycan, and sulfatides was dependent upon both shared and unique contributions from basic residues distributed in several clusters on the surface of LG4. For heparin, the greatest contribution was detected from two clusters, ²⁷¹⁹RKR and ²⁷⁹¹KRK. Binding to -dystroglycan was particularly dependent on basic residues within ²⁷¹⁹RKR, ²⁸³¹RAR, and ²⁸⁵⁸KDR. Binding to galactosylsulfatide was most affected by mutations in ²⁸³¹RAR and ²⁷⁶⁶KGRTK but not in ²⁷¹⁹RKR. The combined analysis of structure and activities reveal differences in LG domain interactions that should enable dissection of biological roles of different laminin ligands.

Received for publication, November 16, 2006 , and in revised form, January 11, 2007.

The atomic coordinates and structure factors (code 2JD4) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by a Wellcome Senior Fellowship (to E. H.) and National Institutes of Health Grant R37-DK36425 (to P. D. Y.). 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 on-line version of this article (available at http://www.jbc.org) contains supplemental Tables 1 and 2.

¹ These two authors contributed equally to this work.

² To whom correspondence should be addressed: Division of Cell and Molecular Biology, Biophysics Section, Blackett Laboratory, Imperial College London SW7 2AZ, London. Tel.: 44-20-7594-7701; Fax: 44-20-7589-0191; E-mail: e.hohenester{at}imperial.ac.uk.

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

This article has been cited by other articles:

				K. K. McKee, S. Capizzi, and P. D. Yurchenco Scaffold-forming and Adhesive Contributions of Synthetic Laminin-binding Proteins to Basement Membrane Assembly J. Biol. Chem., March 27, 2009; 284(13): 8984 - 8994. [Abstract] [Full Text] [PDF]

				N. Ichikawa, K. Iwabuchi, H. Kurihara, K. Ishii, T. Kobayashi, T. Sasaki, N. Hattori, Y. Mizuno, K. Hozumi, Y. Yamada, et al. Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for neurite outgrowth J. Cell Sci., January 15, 2009; 122(2): 289 - 299. [Abstract] [Full Text] [PDF]

				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]

				M. M. S. Barroso, E. Freire, G. S. C. S. Limaverde, G. M. Rocha, E. J. O. Batista, G. Weissmuller, L. R. Andrade, and T. Coelho-Sampaio Artificial Laminin Polymers Assembled in Acidic pH Mimic Basement Membrane Organization J. Biol. Chem., April 25, 2008; 283(17): 11714 - 11720. [Abstract] [Full Text] [PDF]

				K. K. McKee, D. Harrison, S. Capizzi, and P. D. Yurchenco Role of Laminin Terminal Globular Domains in Basement Membrane Assembly J. Biol. Chem., July 20, 2007; 282(29): 21437 - 21447. [Abstract] [Full Text] [PDF]