PDBsum entry 6v4c

Protein binding

PDB id: 6v4c

Contents

Protein chain

294 a.a.

Ligands

ADP

GOL ×4

ETX ×2

PEG

EDO ×2

Metals

_ZN ×2

Waters ×124

PDB id:

6v4c

Name:

Protein binding

Title:

Culex quinquefasciatus d7 long form 1- cxd7l1 in complex with adp

Structure:

Long form d7clu1 salivary protein. Chain: a. Synonym: cxd7l1. Engineered: yes

Source:

Culex quinquefasciatus. Southern house mosquito. Organism_taxid: 7176. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.97Å R-factor: 0.215 R-free: 0.235

Authors:

E.Calvo,D.N.Garboczi,I.Martin-Martin,A.G.Gittis

Key ref:

I.Martin-Martin et al. (2020). ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals. Nat Commun, 11, 2911. PubMed id: 32518308 DOI: 10.1038/s41467-020-16665-z

Date:

27-Nov-19 Release date: 24-Jun-20

Protein chain

A0A1S4K3K8  (D7L1_CULQU) -  Long form salivary protein D7L1 from Culex quinquefasciatus

Seq: 311 a.a.

Struc: 294 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1038/s41467-020-16665-z

Nat Commun 11:2911 (2020)

PubMed id: 32518308

ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals.

I.Martin-Martin, A.Paige, P.C.Valenzuela Leon, A.G.Gittis, O.Kern, B.Bonilla, A.C.Chagas, S.Ganesan, L.B.Smith, D.N.Garboczi, E.Calvo.

ABSTRACT

During blood-feeding, mosquito saliva is injected into the skin to facilitate blood meal acquisition. D7 proteins are among the most abundant components of the mosquito saliva. Here we report the ligand binding specificity and physiological relevance of two D7 long proteins from Culex quinquefasciatus mosquito, the vector of filaria parasites or West Nile viruses. CxD7L2 binds biogenic amines and eicosanoids. CxD7L1 exhibits high affinity for ADP and ATP, a binding capacity not reported in any D7. We solve the crystal structure of CxD7L1 in complex with ADP to 1.97 Å resolution. The binding pocket lies between the two protein domains, whereas all known D7s bind ligands either within the N- or the C-terminal domains. We demonstrate that these proteins inhibit hemostasis in ex vivo and in vivo experiments. Our results suggest that the ADP-binding function acquired by CxD7L1 evolved to enhance blood-feeding in mammals, where ADP plays a key role in platelet aggregation.