5CSD

Ligand binding domain 2 of Penicillium marneffei MP1 protein in complex with arachidonic acids


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

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

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

(2017) Cell Chem Biol 24: 182-194

  • DOI: https://doi.org/10.1016/j.chembiol.2016.12.014
  • Primary Citation of Related Structures:  
    5CSD, 5FB7

  • PubMed 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.


  • Organizational Affiliation

    State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China; Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China; Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China; Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong SAR, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein
A, B, C, D
159Talaromyces marneffei PM1Mutation(s): 0 
Gene Names: GQ26_0022220
UniProt
Find proteins for A0A093VKV7 (Talaromyces marneffei PM1)
Explore A0A093VKV7 
Go to UniProtKB:  A0A093VKV7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A093VKV7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
ACD Binding MOAD:  5CSD Kd: 64 (nM) from 1 assay(s)
BindingDB:  5CSD -TΔS: min: 8.06, max: 26.98 (kJ/mol) from 4 assay(s)
ΔH: min: -6.07e+1, max: -3.90e+1 (kJ/mol) from 4 assay(s)
ΔG: min: -5.13e+1, max: -3.22e+1 (kJ/mol) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.182 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.502α = 90
b = 100.052β = 90.01
c = 99.05γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata collection
SCALEPACKdata scaling
PHASERphasing
PDB_EXTRACTdata extraction
Cootmodel building
Blu-Icedata collection

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-07-27
    Type: Initial release
  • Version 1.1: 2017-02-01
    Changes: Database references
  • Version 1.2: 2017-03-08
    Changes: Database references
  • Version 1.3: 2024-03-20
    Changes: Data collection, Database references, Refinement description