PDBsum entry 5csd

Lipid binding protein

PDB id: 5csd

Contents

Protein chains

158 a.a.

Ligands

ACD ×6

GOL ×2

Waters ×657

PDB id:

5csd

Name:

Lipid binding protein

Title:

Ligand binding domain 2 of penicillium marneffei mp1 protein in complex with arachidonic acids

Structure:

Envelope glycoprotein. Chain: a, b, c, d. Fragment: unp residues 187-345. Engineered: yes

Source:

Talaromyces marneffei pm1. Organism_taxid: 1077442. Gene: gq26_0022220. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.45Å R-factor: 0.182 R-free: 0.204

Authors:

W.H.Lam,H.Zhang,Q.Hao

Key ref:

K.H.Sze et al. (2017). Talaromyces marneffei Mp1p Is a Virulence Factor that Binds and Sequesters a Key Proinflammatory Lipid to Dampen Host Innate Immune Response. Cell Chem Biol, 24, 182-194. PubMed id: 28111099 DOI: 10.1016/j.chembiol.2016.12.014

Date:

23-Jul-15 Release date: 27-Jul-16

Protein chains

A0A093VKV7  (A0A093VKV7_TALMA) -  Envelope glycoprotein from Talaromyces marneffei PM1

Seq: 455 a.a.

Struc: 158 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.chembiol.2016.12.014

Cell Chem Biol 24:182-194 (2017)

PubMed id: 28111099

Talaromyces marneffei Mp1p Is a Virulence Factor that Binds and Sequesters a Key Proinflammatory Lipid to Dampen Host Innate Immune Response.

K.H.Sze, W.H.Lam, H.Zhang, Y.H.Ke, M.K.Tse, P.C.Woo, S.K.Lau, C.C.Lau, J.P.Cai, E.T.Tung, R.K.Lo, S.Xu, R.Y.Kao, Q.Hao, K.Y.Yuen.

ABSTRACT

Talaromyces (Penicillium) marneffei is one of the leading causes of systemic mycosis in immunosuppressed or AIDS patients in Southeast Asia. How this intracellular pathogen evades the host immune defense remains unclear. We provide evidence that T. marneffei depletes levels of a key proinflammatory lipid mediator arachidonic acid (AA) to evade the host innate immune defense. Mechanistically, an abundant secretory mannoprotein Mp1p, shown previously to be a virulence factor, does so by binding AA with high affinity via a long hydrophobic central cavity found in the LBD2 domain. This sequesters a critical proinflammatory signaling lipid, and we see evidence that AA, AA's downstream metabolites, and the cytokines interleukin-6 and tumor necrosis factor α are downregulated in T. marneffei-infected J774 macrophages. Given that Mp1p-LBD2 homologs are identified in other fungal pathogens, we expect that this novel class of fatty-acid-binding proteins sequestering key proinflammatory lipid mediators represents a general virulence mechanism of pathogenic fungi.