Dynamic interaction of the measles virus hemagglutinin with its receptor signaling lymphocytic activation molecule (SLAM, CD150).
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.
Navaratnarajah
Chanakha K
CK
Department of Molecular Medicine and Virology and Gene Therapy Graduate Track, Mayo Clinic, Rochester, Minnesota 55905, USA.
Vongpunsawad
Sompong
S
Oezguen
Numan
N
Stehle
Thilo
T
Braun
Werner
W
Hashiguchi
Takao
T
Maenaka
Katsumi
K
Yanagi
Yusuke
Y
Cattaneo
Roberto
R
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D002144:Callithrix; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000378:metabolism; D007532:Isoleucine / Q000737:chemistry; D008459:Measles virus / Q000378:metabolism*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; D006389:Hemagglutinins, Viral; D011956:Receptors, Cell Surface; D007532:Isoleucine; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1