PDBsum entry 5fft

Sugar binding protein

PDB id: 5fft

Contents

Protein chain

143 a.a.

Metals

_CA

Waters ×114

PDB id:

5fft

Name:

Sugar binding protein

Title:

Crystal structure of surfactant protein-a y221a mutant

Structure:

Pulmonary surfactant-associated protein a. Chain: a. Fragment: neck and carbohydrate recognition domain. Synonym: sp-a. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: sftpa1, sftp-1, sftp1, sftpa. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

2.20Å R-factor: 0.173 R-free: 0.207

Authors:

B.C.Goh,H.Wu,M.J.Rynkiewicz,K.Schulten,B.A.Seaton,F.X.Mccormack

Key ref:

B.C.Goh et al. (2016). Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations. Biochemistry, 55, 3692-3701. PubMed id: 27324153 DOI: 10.1021/acs.biochem.6b00048

Date:

18-Dec-15 Release date: 06-Jul-16

Protein chain

P08427  (SFTPA_RAT) -  Pulmonary surfactant-associated protein A from Rattus norvegicus

Seq: 248 a.a.

Struc: 143 a.a.*

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

DOI no: 10.1021/acs.biochem.6b00048

Biochemistry 55:3692-3701 (2016)

PubMed id: 27324153

Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations.

B.C.Goh, H.Wu, M.J.Rynkiewicz, K.Schulten, B.A.Seaton, F.X.McCormack.

ABSTRACT

Surfactant protein A (SP-A) is a collagenous C-type lectin (collectin) that is critical for pulmonary defense against inhaled microorganisms. Bifunctional avidity of SP-A for pathogen-associated molecular patterns (PAMPs) such as lipid A and for dipalmitoylphosphatidylcholine (DPPC), the major component of surfactant membranes lining the air-liquid interface of the lung, ensures that the protein is poised for first-line interactions with inhaled pathogens. To improve our understanding of the motifs that are required for interactions with microbes and surfactant structures, we explored the role of the tyrosine-rich binding surface on the carbohydrate recognition domain of SP-A in the interaction with DPPC and lipid A using crystallography, site-directed mutagenesis, and molecular dynamics simulations. Critical binding features for DPPC binding include a three-walled tyrosine cage that binds the choline headgroup through cation-π interactions and a positively charged cluster that binds the phosphoryl group. This basic cluster is also critical for binding of lipid A, a bacterial PAMP and target for SP-A. Molecular dynamics simulations further predict that SP-A binds lipid A more tightly than DPPC. These results suggest that the differential binding properties of SP-A favor transfer of the protein from surfactant DPPC to pathogen membranes containing appropriate lipid PAMPs to effect key host defense functions.