PDBsum entry 4tpv

Blood clotting

PDB id: 4tpv

Contents

Protein chains

182 a.a.

Ligands

GOL

Waters ×370

PDB id:

4tpv

Name:

Blood clotting

Title:

Crystal structure of hookworm platelet inhibitor

Structure:

Platelet inhibitor. Chain: a, b. Engineered: yes

Source:

Ancylostoma caninum. Dog hookworm. Organism_taxid: 29170. Gene: hpi. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.152 R-free: 0.194

Authors:

J.F.Andersen,D.Ma,I.Francischetti

Key ref:

D.Ma et al. (2015). The structure of hookworm platelet inhibitor (HPI), a CAP superfamily member from Ancylostoma caninum. Acta Crystallogr F Struct Biol Commun, 71, 643-649. PubMed id: 26057788 DOI: 10.1107/S2053230X1500271X

Date:

09-Jun-14 Release date: 22-Apr-15

Protein chains

Q962V9  (HPI_ANCCA) -  Hookworm platelet inhibitor 1 from Ancylostoma caninum

Seq: 198 a.a.

Struc: 182 a.a.

DOI no: 10.1107/S2053230X1500271X

Acta Crystallogr F Struct Biol Commun 71:643-649 (2015)

PubMed id: 26057788

The structure of hookworm platelet inhibitor (HPI), a CAP superfamily member from Ancylostoma caninum.

D.Ma, I.M.Francischetti, J.M.Ribeiro, J.F.Andersen.

ABSTRACT

Secreted protein components of hookworm species include a number of representatives of the cysteine-rich/antigen 5/pathogenesis-related 1 (CAP) protein family known as Ancylostoma-secreted proteins (ASPs). Some of these have been considered as candidate antigens for the development of vaccines against hookworms. The functions of most CAP superfamily members are poorly understood, but one form, the hookworm platelet inhibitor (HPI), has been isolated as a putative antagonist of the platelet integrins αIIbβ3 and α2β1. Here, the crystal structure of HPI is described and its structural features are examined in relation to its possible function. The HPI structure is similar to those of other ASPs and shows incomplete conservation of the sequence motifs CAP1 and CAP2 that are considered to be diagnostic of CAP superfamily members. The asymmetric unit of the HPI crystal contains a dimer with an extensive interaction interface, but chromatographic measurements indicate that it is primarily monomeric in solution. In the dimeric structure, the putative active-site cleft areas from both monomers are united into a single negatively charged depression. A potential Lys-Gly-Asp disintegrin-like motif was identified in the sequence of HPI, but is not positioned at the apex of a tight turn, making it unlikely that it interacts with the integrin. Recombinant HPI produced in Escherichia coli was found not to inhibit the adhesion of human platelets to collagen or fibrinogen, despite having a native structure as shown by X-ray diffraction. This result corroborates previous analyses of recombinant HPI and suggests that it might require post-translational modification or have a different biological function.