PDBsum entry 1xar

Sugar binding protein

PDB id: 1xar

Contents

Protein chain

146 a.a. *

Metals

_NA ×4

Waters ×77

* Residue conservation analysis

PDB id:

1xar

Name:

Sugar binding protein

Title:

Crystal structure of a fragment of dc-signr (containing the carbohydrate recognition domain and two repeats of the neck).

Structure:

Cd209 antigen-like protein 1. Chain: a, b. Fragment: sequence database residues 216-399. Synonym: dendritic cell-specific icam-3-grabbing nonintegrin 2, dc- sign2, dc-sign related protein, dc-signr, liver/lymph node-specific icam-3-grabbing nonintegrin, l-sign. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cd209l, cd209l1

Resolution:

2.25Å R-factor: 0.222 R-free: 0.249

Authors:

H.Feinberg,Y.Guo,D.A.Mitchell,K.Drickamer,W.I.Weis

Key ref:

H.Feinberg et al. (2005). Extended neck regions stabilize tetramers of the receptors DC-SIGN and DC-SIGNR. J Biol Chem, 280, 1327-1335. PubMed id: 15509576 DOI: 10.1074/jbc.M409925200

Date:

26-Aug-04 Release date: 16-Nov-04

Protein chains

Q9H2X3  (CLC4M_HUMAN) -  C-type lectin domain family 4 member M from Homo sapiens

Seq: 399 a.a.

Struc: 146 a.a.

DOI no: 10.1074/jbc.M409925200

J Biol Chem 280:1327-1335 (2005)

PubMed id: 15509576

Extended neck regions stabilize tetramers of the receptors DC-SIGN and DC-SIGNR.

H.Feinberg, Y.Guo, D.A.Mitchell, K.Drickamer, W.I.Weis.

ABSTRACT

The human cell surface receptors DC-SIGN (dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin) and DC-SIGNR (DC-SIGN-related) bind to oligosaccharide ligands found on human tissues as well as on pathogens including viruses, bacteria, and parasites. The extracellular portion of each receptor contains a membrane-distal carbohydrate-recognition domain (CRD) and forms tetramers stabilized by an extended neck region consisting of 23 amino acid repeats. Cross-linking analysis of full-length receptors expressed in fibroblasts confirms the tetrameric state of the intact receptors. Hydrodynamic studies on truncated receptors demonstrate that the portion of the neck of each protein adjacent to the CRD is sufficient to mediate the formation of dimers, whereas regions near the N terminus are needed to stabilize the tetramers. Some of the intervening repeats are missing from polymorphic forms of DC-SIGNR. Two different crystal forms of truncated DC-SIGNR comprising two neck repeats and the CRD reveal that the CRDs are flexibly linked to the neck, which contains alpha-helical segments interspersed with non-helical regions. Differential scanning calorimetry measurements indicate that the neck and CRDs are independently folded domains. Based on the crystal structures and hydrodynamic data, models for the full extracellular domains of the receptors have been generated. The observed flexibility of the CRDs in the tetramer, combined with previous data on the specificity of these receptors, suggests an important role for oligomerization in the recognition of endogenous glycans, in particular those present on the surfaces of enveloped viruses recognized by these proteins.

Selected figure(s)

Figure 5.
FIG. 5. Tetramer crystal structure. A, tetramer crystal structure for truncated DC-SIGNR comprising the CRD and two full neck repeats. Application of a crystallographic 2-fold rotation to the two monomers in the asymmetric unit generates the tetramer. The two protomers in an asymmetric unit are shown in red and cyan. B, close-up view of the parallel four-helix bundle. The side chains of the conserved hydrophobic heptad residues are shown in ball-and-stick representation. C, superposition of the monomer B neck helix onto that of monomer A showing the asymmetrically disposed CRDs.

Figure 6.
FIG. 6. Flexibility in the CRD-neck junction. A, superposition of the dimer structure on the tetramer structure. The superposition was done by overlapping the CRD-proximal neck helix of one protomer of the dimer (red) onto one of the tetramer (cyan). B, superposition of protomer B of the dimer (blue) onto protomer A of the tetramer (green). The crystallographic 2-fold symmetry of the tetramer form was then applied to generate the tetramer and a second copy of the superimposed dimer.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 1327-1335) copyright 2005.

Figures were selected by an automated process.