Distinct Kinetics for Binding of the CD46 and SLAM Receptors to Overlapping Sites in the Measles Virus Hemagglutinin Protein

Santiago, César; Björling, Ewa; Stehle, Thilo; Casasnovas, José M.

doi:10.1074/jbc.m202973200

Cited by 64 publications

(64 citation statements)

References 37 publications

(37 reference statements)

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“…The surface plasmon resonance-binding study using these soluble proteins provided definitive evidence that, unlike MV-H (Ed), MV-H (WT) fails to bind CD46, whereas both MV-H (WT) and MV-H (Ed) proteins bind SLAM with similar affinities (K d of 0.29 and 0.43 M, respectively) and k on and k off rates ( Table 1). The results are consistent with functional assays as well as a previous binding study reporting a K d value of 0.27 M for the SLAM-MV-H (Ed) interaction (14).…”

Section: Resultssupporting

confidence: 81%

“…Functional studies based on virus infection have shown that the Edmonston (Ed) vaccine strain of MV uses both SLAM and CD46 as receptors (11,12), whereas most WT strains of MV use only SLAM (8,13). Biochemical studies of MV-H-receptor interaction, however, have been performed only with MV-H (Ed) (14), not MV-H (WT). We have produced the soluble head domains (residues 149-617) of MV-H (Ed) and MV-H (WT) proteins by transfecting HEK293S cells lacking N-acetylglucosaminyltransferase I (GnTI) activity (15) with expression plasmids encoding the respective molecules [see supporting information (SI) Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, the SLAMbinding site includes the reported epitopes of neutralizing antibodies. Escape mutants from mAb 55 that neutralizes the SLAM-dependent MV infection had an R533G substitution (23), whereas those from I-41 that blocks MV-H binding to SLAM had an F552V substitution (14,20) (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

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Crystal structure of measles virus hemagglutinin provides insight into effective vaccines

Hanabusa¹,

Kajikawa

Maita

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

221

260

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Measles still remains a major cause of childhood morbidity and mortality worldwide. Measles virus (MV) vaccines are highly successful, but the mechanism underlying their efficacy has been unclear. Here we report the crystal structure of the MV attachment protein, hemagglutinin, responsible for MV entry. The receptorbinding head domain exhibits a cubic-shaped ␤-propeller structure and forms a homodimer. N-linked sugars appear to mask the broad regions and cause the two molecules forming the dimer to tilt oppositely toward the horizontal plane. Accordingly, residues of the putative receptor-binding site, highly conserved among MV strains, are strategically positioned in the unshielded area of the protein. These conserved residues also serve as epitopes for neutralizing antibodies, ensuring the serological monotype, a basis for effective MV vaccines. Our findings suggest that sugar moieties in the MV hemagglutinin critically modulate virus-receptor interaction as well as antiviral antibody responses, differently from sugars of the HIV gp120, which allow for immune evasion.x-ray crystallography paramyxovirus ͉ morbillivirus ͉ SLAM ͉ infectious disease ͉ paramyxovirus

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Crystal structure of measles virus hemagglutinin provides insight into effective vaccines

Hanabusa¹,

Kajikawa

Maita

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

221

260

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“…The affinity between H and SLAM reported in our study is up to five times stronger than that reported previously (80 versus 400 nM) (29,30). The stronger association we observe between H and SLAM as compared with these previous studies may be explained by the fact that we used a sH construct which comprised the complete H ectodomain (residues 60 -617) as opposed to a truncated form (residues 149 -617).…”

Section: I194s But Not the Quartet Of Mutations In ␤-Sheet 5 Ablatecontrasting

confidence: 54%

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

Navaratnarajah

Vongpunsawad

Oezguen

et al. 2008

Journal of Biological Chemistry

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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.Measles is a leading cause of childhood morbidity and mortality in developing countries (1). The immune suppression that accompanies infection with wild-type measles viruses (MV) 2 exposes individuals to secondary infections causing most of the fatalities associated with the disease (2). Live attenuated MV vaccines have effectively reduced the morbidity and mortality of measles world-wide (3). The difference in pathology between the wild-type and vaccine strains is in part explained by the receptors used for cell entry. Wild-type MV uses the signaling lymphocyte activation molecule (SLAM, CD150) (4 -7), while the vaccine strain has gained the ability to also use the ubiquitous protein CD46 (8 -10). SLAM-targeting accounts for lymphotropism and is central to understanding MV tropism and disease progression.Receptor attachment of MV and the other morbilliviruses is mediated by hemagglutinin (H) homodimers. Unlike other members of the Paramyxoviridae, the morbillivirus H-proteins do not have neuraminidase activity. Upon receptor attachment, H induces conformational changes in the trimeric fusion (F) protein, resulting in the fusion of viral and cellular membranes (11,12). MV H is a 617-amino acid type II transmembrane glycoprotein, which is comprised of an N-terminal cytoplasmic tail, a membrane-spanning domain, and an extracellular stalk region connected to a C-terminal globular head (13).Previously, we generated a three-dimensional model of the extracellular domain of the MV H-protein based on the crystal structure of Newcastle Disease Virus (NDV) HN (hemagglutinin neuraminidase) protein (sequence identity of 12%), a related paramyxovirus (14,15). This model predicts that the MV H ectodomain has a 6-blade propeller structure....

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“…The pathogenic wild-type MV (which is not selectively oncolytic) uses primarily signaling lymphocyte activation molecule, expressed on activated T cells, B cells, and monocytes/macrophages, as a receptor (18,19). In contrast, attenuated vaccine strains such as MV-Edm use predominantly CD46 (20), which is ubiquitously expressed (usually at low density) by all human cells except erythrocytes (21). In addition, CD46 is required to mediate intercellular fusion.…”

Section: Introductionmentioning

confidence: 99%

High CD46 Receptor Density Determines Preferential Killing of Tumor Cells by Oncolytic Measles Virus

Anderson¹,

Nakamura²,

et al. 2004

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Distinct Kinetics for Binding of the CD46 and SLAM Receptors to Overlapping Sites in the Measles Virus Hemagglutinin Protein

Abstract: Measles virus (MV) is

Cited by 64 publications

References 37 publications

Crystal structure of measles virus hemagglutinin provides insight into effective vaccines

Crystal structure of measles virus hemagglutinin provides insight into effective vaccines

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

High CD46 Receptor Density Determines Preferential Killing of Tumor Cells by Oncolytic Measles Virus

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