PDBsum entry 3d34

Immune system

PDB id: 3d34

Contents

Protein chain

211 a.a. *

Metals

_CA ×2

_NI ×6

Waters ×319

* Residue conservation analysis

PDB id:

3d34

Name:

Immune system

Title:

Structure of the f-spondin domain of mindin

Structure:

Spondin-2. Chain: a, b. Fragment: f-spondin domain, unp residues 27-249. Synonym: mindin, differentially expressed in cancerous and non- cancerous lung cells 1, dil-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: spon2, dil1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.80Å R-factor: 0.189 R-free: 0.215

Authors:

Y.Li,R.A.Mariuzza

Key ref:

Y.Li et al. (2009). Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule. Embo J, 28, 286-297. PubMed id: 19153605

Date:

09-May-08 Release date: 17-Feb-09

Protein chains

Q9BUD6  (SPON2_HUMAN) -  Spondin-2 from Homo sapiens

Seq: 331 a.a.

Struc: 211 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Embo J 28:286-297 (2009)

PubMed id: 19153605

Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule.

Y.Li, C.Cao, W.Jia, L.Yu, M.Mo, Q.Wang, Y.Huang, J.M.Lim, M.Ishihara, L.Wells, P.Azadi, H.Robinson, Y.W.He, L.Zhang, R.A.Mariuzza.

ABSTRACT

Mindin (spondin-2) is an extracellular matrix protein of unknown structure that is required for efficient T-cell priming by dendritic cells. Additionally, mindin functions as a pattern recognition molecule for initiating innate immune responses. These dual functions are mediated by interactions with integrins and microbial pathogens, respectively. Mindin comprises an N-terminal F-spondin (FS) domain and C-terminal thrombospondin type 1 repeat (TSR). We determined the structure of the FS domain at 1.8-A resolution. The structure revealed an eight-stranded antiparallel beta-sandwich motif resembling that of membrane-targeting C2 domains, including a bound calcium ion. We demonstrated that the FS domain mediates integrin binding and identified the binding site by mutagenesis. The mindin FS domain therefore represents a new integrin ligand. We further showed that mindin recognizes lipopolysaccharide (LPS) through its TSR domain, and obtained evidence that C-mannosylation of the TSR influences LPS binding. Through these dual interactions, the FS and TSR domains of mindin promote activation of both adaptive and innate immune responses.