PDBsum entry 2c3a

Viral protein

PDB id: 2c3a

Contents

Protein chains

253 a.a. *

274 a.a. *

Ligands

NAG-NAG ×2

Metals

_ZN ×5

_CL ×2

_NA ×2

Waters ×53

* Residue conservation analysis

PDB id:

2c3a

Name:

Viral protein

Title:

Structure of unliganded hsv gd reveals a mechanism for receptor- mediated activation of virus entry

Structure:

Glycoprotein d. Chain: a, b. Engineered: yes. Mutation: yes. Other_details: n-acetyl-d-glucosamine linked to asn94 for both chains a and b

Source:

Human herpesvirus 1. Human herpes simplex virus 1. Organism_taxid: 10298. Strain: patton. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

2.50Å R-factor: 0.228 R-free: 0.275

Authors:

C.Krummenacher,V.M.Supekar,J.C.Whitbeck,E.Lazear,S.A.Connolly, R.J.Eisenberg,G.H.Cohen,D.C.Wiley,A.Carfi

Key ref:

C.Krummenacher et al. (2005). Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry. EMBO J, 24, 4144-4153. PubMed id: 16292345 DOI: 10.1038/sj.emboj.7600875

Date:

05-Oct-05 Release date: 21-Dec-05

Protein chain

P57083  (GD_HHV1P) -  Envelope glycoprotein D from Human herpesvirus 1 (strain Patton)

Seq: 394 a.a.

Struc: 253 a.a.*

Protein chain

P57083  (GD_HHV1P) -  Envelope glycoprotein D from Human herpesvirus 1 (strain Patton)

Seq: 394 a.a.

Struc: 274 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1038/sj.emboj.7600875

EMBO J 24:4144-4153 (2005)

PubMed id: 16292345

Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry.

C.Krummenacher, V.M.Supekar, J.C.Whitbeck, E.Lazear, S.A.Connolly, R.J.Eisenberg, G.H.Cohen, D.C.Wiley, A.Carfí.

ABSTRACT

Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C-terminal residues. The structure reveals that the C-terminus is anchored near the N-terminal region and masks receptor-binding sites. Locking the C-terminus in the position observed in the crystals by an intramolecular disulfide bond abolished receptor binding and virus entry, demonstrating that this region of gD moves upon receptor binding. Similarly, a point mutant that would destabilize the C-terminus structure was nonfunctional for entry, despite increased affinity for receptors. We propose that a controlled displacement of the gD C-terminus upon receptor binding is an essential feature of HSV entry, ensuring the timely activation of membrane fusion.

Selected figure(s)

Figure 1.
Figure 1 gD(23-306)[307C] structure. (A) Schematic representation of HSV-1 gD. Disulfide bonds are shown as black lines and N-linked oligosaccharides as lollipops. Colors of the N-terminal region, forming the HVEM-binding hairpin in the gD285-HVEM complex, the Ig-like core, and the C-terminal region past residue 255 are represented in green, yellow, and red, respectively. Positions of important amino acids and domain boundaries are numbered according to the mature form of gD. TM: transmembrane region. (B) Ribbon representation of the gD(23-306)[307C] subunit. The secondary structure elements are labeled as in Carfi et al (2001). The color code used is same as in (A). (C) As in (B) after 180° rotation as indicated. (D) Front view of gD(23-306)[307C] structure. The model is rotated 90° clockwise with respect to panel B to show the front side of gD, where the N- and C-terminal regions interact. (E) Front view of gD285 from the gD285-HVEM complex, with HVEM removed for clarity. (F) Front view of gD285 in the unbound state.

Figure 6.
Figure 6 Proposed mechanism for receptor-mediated activation of HSV gD. Envelope gD is shown, as a putative dimer, in its unbound state as well as during interaction with HVEM (top) or nectin-1 (bottom). Conformational changes are chronologically indicated by numbered arrows: (1) displacement of the C-terminus, (2) folding of the gD N-terminus in the case of HVEM binding, and (3) exposure of the PFD. The N-terminus of gD is shown in green, the C-terminus (290-299) is colored red, and the PFD (260-285) is pink.

The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2005, 24, 4144-4153) copyright 2005.

Figures were selected by the author.