PDBsum entry 3inb

Viral protein/immune system

PDB id: 3inb

Contents

Protein chains

389 a.a.

126 a.a. *

Ligands

NAG ×6

SO4 ×3

Waters ×8

* Residue conservation analysis

PDB id:

3inb

Name:

Viral protein/immune system

Title:

Structure of the measles virus hemagglutinin bound to the cd46 receptor

Structure:

Hemagglutinin glycoprotein. Chain: a, b. Fragment: head domain, residues 179-617. Engineered: yes. Membrane cofactor protein. Chain: c, d. Fragment: sushi domains 1 and 2, residues 35-160. Synonym: trophoblast leukocyte common antigen, tlx. Engineered: yes

Source:

Measles virus strain edmonston. Viruses. Organism_taxid: 11235. Strain: edmonston. Gene: h. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: ovary cells. Homo sapiens.

Resolution:

3.10Å R-factor: 0.228 R-free: 0.259

Authors:

C.Santiago,M.L.Celma,T.Stehle,J.M.Casasnovas

Key ref:

C.Santiago et al. (2010). Structure of the measles virus hemagglutinin bound to the CD46 receptor. Nat Struct Biol, 17, 124-129. PubMed id: 20010840 DOI: 10.1038/nsmb.1726

Date:

12-Aug-09 Release date: 22-Dec-09

Protein chains

P08362  (HEMA_MEASE) -  Hemagglutinin glycoprotein from Measles virus (strain Edmonston)

Seq: 617 a.a.

Struc: 389 a.a.*

Protein chains

P15529  (MCP_HUMAN) -  Membrane cofactor protein from Homo sapiens

Seq: 392 a.a.

Struc: 126 a.a.

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1038/nsmb.1726

Nat Struct Biol 17:124-129 (2010)

PubMed id: 20010840

Structure of the measles virus hemagglutinin bound to the CD46 receptor.

C.Santiago, M.L.Celma, T.Stehle, J.M.Casasnovas.

ABSTRACT

The highly contagious measles virus infects millions of individuals worldwide, causing serious disease in children of developing countries. Infection is initiated by attachment of the measles virus hemagglutinin (MV-H), a glycoprotein anchored to the virus envelope, to the host cell receptors CD46 or signaling lymphocyte activation molecule (SLAM). Here we report the crystal structure of MV-H in complex with a CD46 protein spanning the two N-terminal domains. A unique groove at the side of the MV-H beta-propeller domain, which is absent in homologous paramyxovirus attachment proteins, engages residues in both CD46 domains. Key contacts involve a protruding loop in the N-terminal CD46 domain that carries two sequential proline residues (PP motif) and penetrates deeply into a hydrophobic socket in MV-H. We identify a similar PP motif in SLAM, defining a common measles virus recognition epitope in the CD46 and SLAM receptor proteins.

Selected figure(s)

Figure 1.
(a) Representation of the dimeric MV-H–CD46 complex present in the asymmetric unit of the crystals. Ribbon drawings of the MV-H molecules are shown with a rainbow coloring scheme, whereas Cα traces of the CD46 molecules are shown in blue. The six β-sheets building the MV-H β-propeller domain are labeled. The C-terminal residues of the molecules, shown as spheres, are followed by a polypeptide stalk in the full-length MV-H protein or the SCR3 and SCR4 domains in the CD46 molecule. Putative location of the virus and cell membranes are shown. (b) Detailed view of the MV-H–CD46 interface. Two side views, differing by 120°, are shown. CD46 residues buried by the interaction with MV-H are shown with spheres colored in dark blue (contact region 1, the D′D loop of SCR1), magenta (contact region 2, the SCR1-SCR2 interdomain region) and light blue (contact region 3, residues at SCR2).

Figure 2.
Ribbon drawing of the three MV-H–CD46 interacting regions described in Figure 1b. CD46 and MV-H are shown in blue and orange, respectively. Buried residues participating in critical contacts are depicted in stick representation and labeled in the three panels, with oxygens and nitrogens shown in red and blue, respectively. Side chains of MV-H residues engaged in hydrogen bonds (black dashed lines) with CD46 are highlighted in magenta, whereas cysteines are yellow. (a) Contact region 1, showing relevant contacts between MV-H and CD46 residues at the D′D loop of SCR1 (Ile37–Leu40). Loops connecting the β-strands s2 and s3 (s2-s3) of blade β4 and the blades β4 and β5 (β4-β5) are marked. (b) Contact region 2, showing interactions of MV-H with the CD46 SCR1-SCR2 interdomain region. This surface includes contacts between MV-H and CD46 residues linking Cys60 in SCR1 and Cys65 in SCR2, as well as the DE loop of SCR2. (c) Contact region 3, showing interactions between MV-H and the SCR2 of CD46. The N-acetylglucosamine (NAG) residue attached to Asn80 of CD46 is shown in stick representation with carbons colored green. Additional contacts are listed in Supplementary Table 1.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2010, 17, 124-129) copyright 2010.

Figures were selected by the author.