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

J. Biol. Chem., Vol. 280, Issue 44, 37236-37245, November 4, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/44/37236    most recent M506753200v1 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 Burgess, B. R. Articles by Garboczi, D. N. Search for Related Content PubMed PubMed Citation Articles by Burgess, B. R. Articles by Garboczi, D. N. Social Bookmarking                      What's this?

Dissection of Merozoite Surface Protein 3, a Representative of a Family of Plasmodium falciparum Surface Proteins, Reveals an Oligomeric and Highly Elongated Molecule^*

Brandt R. Burgess, Peter Schuck, and David N. Garboczi1

From the Structural Biology Section, Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and the Division of Bioengineering and Physical Science, Office of the Director, Office of Research Services, National Institutes of Health, Bethesda, Maryland 20892

Vaccination with the merozoite surface protein 3 (MSP3) of Plasmodium falciparum protects against infection in primates and is under development as a vaccine against malaria in humans. MSP3 is secreted and associates with the parasite membrane but lacks a predicted transmembrane domain or a glycosylphosphatidylinositol anchor. Its role in the invasion of red blood cells is unclear. To study MSP3, we produced recombinant full-length protein and found by size exclusion chromatography that the apparent size of MSP3 was much larger than predicted from its sequence. To investigate this, we used several biophysical techniques to characterize the full-length molecule and four smaller polypeptides. The MSP3 polypeptides contain a large amount of -helix and random coil secondary structure as measured by circular dichroism spectroscopy. The full-length MSP3 forms highly elongated dimers and tetramers as revealed by chemical cross-linking and analytical ultracentrifugation. The dimer is formed through a leucine zipper-like domain located between residues 306 and 362 at the C terminus. Two dimers interact through their C termini to form a tetramer with an apparent association constant of 3 µM. Sedimentation velocity experiments determined that the MSP3 molecules are highly extended in solution (some with f/f₀ > 2). These data, in light of the recent discoveries of three other Plasmodium proteins containing very similar C-terminal sequences, suggest that the members of this newly identified family may adopt highly extended and oligomeric novel structures capable of interacting with a red blood cell at relatively long distances.

Received for publication, June 21, 2005 , and in revised form, August 19, 2005.

^* This work was supported by the Intramural Research Program of the NIAID, National Institutes of Health. 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 Figs. S1-S3.

¹ To whom correspondence should be addressed: Structural Biology Section, NIAID, Twinbrook II, 12441 Parklawn Dr., Rockville, MD 20852. Tel.: 301-496-4773; Fax: 301-402-0284; E-mail: dgarboczi{at}niaid.nih.gov.

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

This article has been cited by other articles:

				S. J. Jordan, O. H. Branch, J. C. Castro, R. A. Oster, and J. C. Rayner Genetic Diversity of the Malaria Vaccine Candidate Plasmodium falciparum Merozoite Surface Protein-3 in a Hypoendemic Transmission Environment Am J Trop Med Hyg, March 1, 2009; 80(3): 479 - 486. [Abstract] [Full Text] [PDF]

				C. W. Kauth, U. Woehlbier, M. Kern, Z. Mekonnen, R. Lutz, N. Mucke, J. Langowski, and H. Bujard Interactions between Merozoite Surface Proteins 1, 6, and 7 of the Malaria Parasite Plasmodium falciparum J. Biol. Chem., October 20, 2006; 281(42): 31517 - 31527. [Abstract] [Full Text] [PDF]

				R. Lundquist, L. K. Nielsen, A. Jafarshad, D. SoeSoe, L. H. Christensen, P. Druilhe, and M. H. Dziegiel Human Recombinant Antibodies against Plasmodium falciparum Merozoite Surface Protein 3 Cloned from Peripheral Blood Leukocytes of Individuals with Immunity to Malaria Demonstrate Antiparasitic Properties. Infect. Immun., June 1, 2006; 74(6): 3222 - 3231. [Abstract] [Full Text] [PDF]