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J. Biol. Chem., Vol. 283, Issue 17, 11763-11771, April 25, 2008

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Dynamic Interaction of the Measles Virus Hemagglutinin with Its Receptor Signaling Lymphocytic Activation Molecule (SLAM, CD150)^*

Chanakha K. Navaratnarajah, Sompong Vongpunsawad, Numan Oezguen, Thilo Stehle^¶, Werner Braun, Takao Hashiguchi^||, Katsumi Maenaka^**, Yusuke Yanagi^||, and Roberto Cattaneo¹

From the Department of Molecular Medicine and Virology and Gene Therapy Graduate Track, Mayo Clinic, Rochester, Minnesota 55905, the Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas 77555, the ^¶Interfakultäres Institut für Biochemie, University of Tübingen, D-72076 Tübingen, Germany and Vanderbilt University School of Medicine, Nashville, Tennessee 37240, and the ^||Department of Virology, Faculty of Medicine and the ^**Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan

The interaction of measles virus with its receptor signaling lymphocytic activation molecule (SLAM) controls cell entry and governs tropism. We predicted potential interface areas of the measles virus attachment protein hemagglutinin to begin the investigation. We then assessed the relevance of individual amino acids located in these areas for SLAM-binding and SLAM-dependent membrane fusion, as measured by surface plasmon resonance and receptor-specific fusion assays, respectively. These studies identified one hemagglutinin protein residue, isoleucine 194, which is essential for primary binding. The crystal structure of the hemagglutinin-protein localizes Ile-194 at the interface of propeller blades 5 and 6, and our data indicate that a small aliphatic side chain of residue 194 stabilizes a protein conformation conducive to binding. In contrast, a quartet of residues previously shown to sustain SLAM-dependent fusion is not involved in binding. Instead, our data prove that after binding, this quartet of residues on propeller blade 5 conducts conformational changes that are receptor-specific. Our study sets a structure-based stage for understanding how the SLAM-elicited conformational changes travel through the H-protein ectodomain before triggering fusion protein unfolding and membrane fusion.

Received for publication, February 4, 2008 , and in revised form, February 19, 2008.

^* This work was supported in part by Grant R01 CA090363 from the National Institutes of Health and the Mayo Foundation. 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 data and Fig. S1.

¹ To whom correspondence should be addressed: 200 1^st St. SW, Guggenheim 1838, Rochester MN 55905. Tel.: 507-538-1188; Fax: 507-266-2122; E-mail: cattaneo.roberto{at}mayo.edu.

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This article has been cited by other articles:

				M. D. Muhlebach, V. H. J. Leonard, and R. Cattaneo The Measles Virus Fusion Protein Transmembrane Region Modulates Availability of an Active Glycoprotein Complex and Fusion Efficiency J. Virol., November 15, 2008; 82(22): 11437 - 11445. [Abstract] [Full Text] [PDF]