PDBsum entry 3d11

Hydrolase

PDB id: 3d11

Contents

Protein chain

427 a.a. *

Ligands

NAG-NAG ×2

NAG-NAG-BMA-BMA-MAN

NAG

Metals

IOD ×19

Waters ×210

* Residue conservation analysis

PDB id:

3d11

Name:

Hydrolase

Title:

Crystal structures of the nipah g attachment glycoprotein

Structure:

Hemagglutinin-neuraminidase. Chain: a. Fragment: unp residues 176-602. Engineered: yes

Source:

Nipah virus. Organism_taxid: 121791. Gene: hn. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.31Å R-factor: 0.228 R-free: 0.257

Authors:

K.Xu,K.R.Rajashankar,Y.P.Chan,P.Himanen,C.C.Broder,D.B.Nikolov

Key ref:

K.Xu et al. (2008). Host cell recognition by the henipaviruses: crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3. Proc Natl Acad Sci U S A, 105, 9953-9958. PubMed id: 18632560 DOI: 10.1073/pnas.0804797105

Date:

02-May-08 Release date: 19-Aug-08

Protein chain

Q9IH62  (GLYCP_NIPAV) -  Glycoprotein G from Nipah virus

Seq: 602 a.a.

Struc: 427 a.a.

Enzyme reactions

• Enzyme class: E.C.3.2.1.18 - exo-alpha-sialidase.
• Reaction: Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)-glycosidic linkages of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.

DOI no: 10.1073/pnas.0804797105

Proc Natl Acad Sci U S A 105:9953-9958 (2008)

PubMed id: 18632560

Host cell recognition by the henipaviruses: crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3.

K.Xu, K.R.Rajashankar, Y.P.Chan, J.P.Himanen, C.C.Broder, D.B.Nikolov.

ABSTRACT

Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound state and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein-protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G beta-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.

Selected figure(s)

Figure 2.
Crystal structure of the NiV-G/ephrin-B3 complex. (A) Side view of the NiV-G/ephrin-B3 complex. The β-strands of NiV-G are colored in magenta, and the α-helices are in cyan. The β-strands of ephrin-B3 are colored in yellow and the α-helices are in red. The carbohydrate moieties, shown as stick models, do not interact with ephrin-B3 but extend in the solvent. The N and C termini of the molecules are labeled. (B) The molecular surfaces of the henipavirus (cyan) and the parainfluenza virus (magenta) attachment proteins along the top (or receptor-binding) face of the molecules. The lower images are close-up views of the receptor-binding pockets with the bound receptor (ephrin-B3 G–H loop in yellow, sialic acid in green). Only the G–H loop of ephrin-B3 is shown. In red are shown the NiV-G residues that interact with ephrin-B3 residues outside of the G–H loop, highlighting the polar region of the NiV-G/ephrin interface.

Figure 5.
Structure of the NiV-G/ephrin interface. Interacting residues are labeled. (A) Salt bridges at the polar (peripheral) region of the NiV-G/ephrin interface. NiV-G is in yellow and ephrin-B3 in gray. (B) The G–H ephrin-B3 loop bound to the NiV-G surface channel. (C) The same surface in the unbound NiV-G molecule. The position of the G–H ephrin-B3 loop is still shown to illustrate that the binding pockets for ephrin residues P122, L124, and W125 are already fully formed in the unbound attachment protein and undergo little or no conformational rearrangements upon ephrin binding. On the other hand, the Y120 binding pocket is only formed upon ephrin binding.

Figures were selected by an automated process.