PDBsum entry 3gpr

Cell adhesion

PDB id: 3gpr

Contents

Protein chains

132 a.a. *

127 a.a. *

134 a.a. *

124 a.a. *

* Residue conservation analysis

PDB id:

3gpr

Name:

Cell adhesion

Title:

Crystal structure of rhodocetin

Structure:

Rhodocetin subunit alpha. Chain: a. Rhodocetin subunit beta. Chain: b. Rhodocetin subunit gamma. Chain: c. Rhodocetin subunit delta. Chain: d

Source:

Calloselasma rhodostoma. Malayan pit viper. Organism_taxid: 8717. Organism_taxid: 8717

Resolution:

3.20Å R-factor: 0.223 R-free: 0.284

Authors:

J.Stetefeld

Key ref:

J.A.Eble et al. (2009). The alpha2beta1 integrin-specific antagonist rhodocetin is a cruciform, heterotetrameric molecule. Faseb J, 23, 2917-2927. PubMed id: 19369383

Date:

23-Mar-09 Release date: 15-Dec-09

Protein chain

P81397  (SLEA_CALRH) -  Snaclec rhodocetin subunit alpha from Calloselasma rhodostoma

Seq: 133 a.a.

Struc: 132 a.a.

Protein chain

P81398  (SLEB_CALRH) -  Snaclec rhodocetin subunit beta from Calloselasma rhodostoma

Seq: 129 a.a.

Struc: 127 a.a.

Protein chain

D2YW39  (SLEC_CALRH) -  Snaclec rhodocetin subunit gamma (Fragment) from Calloselasma rhodostoma

Seq: 135 a.a.

Struc: 134 a.a.*

Protein chain

D2YW40  (SLED_CALRH) -  Snaclec rhodocetin subunit delta from Calloselasma rhodostoma

Seq: 124 a.a.

Struc: 124 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Faseb J 23:2917-2927 (2009)

PubMed id: 19369383

The alpha2beta1 integrin-specific antagonist rhodocetin is a cruciform, heterotetrameric molecule.

J.A.Eble, S.Niland, T.Bracht, M.Mormann, J.Peter-Katalinic, G.Pohlentz, J.Stetefeld.

ABSTRACT

The integrin alpha2beta1 plays an important role in various pathophysiological processes, such as thrombosis, wound healing, inflammation, and metastasis. Rhodocetin, a constituent of the venom of the hemorrhagic Malayan pit viper (Calloselasma rhodostoma), is a specific alpha2beta1 integrin antagonist. To understand its molecular mode of action, its structure was studied by crystallography. Its quaternary structure in solution was also analyzed biochemically. Two novel subunits of rhodocetin were sequenced by mass spectrometry. Their integrin binding was measured by protein interaction ELISAs. Rhodocetin is a C-type lectin-like protein (CLP) consisting of four homologous, yet distinct, subunits, alpha, beta, gamma, and delta, the latter two of which have been unknown to date. With their CLP folds and loop-swapping motifs, the subunits alpha, beta and gamma, delta form two heterodimeric pairs. Uniquely, they arrange orthogonally and shape a cruciform molecule. Bearing a single unpaired cysteine residue, rhodocetin can only form covalent supramolecular complexes with a maximum aggregation number of 2, unlike many heterodimeric CLPs. Being the first heterotetrameric CLP to be crystallized, rhodocetin provides not only the prototypic molecular structure for heterotetrameric CLPs, but also a lead structure for pharmaceutical alpha2beta1 integrin antagonists.