5ECF

Ligand binding domain 1 of Penicillium marneffei MP1 protein complexed with arachidonic acids


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.256 
  • R-Value Observed: 0.258 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history


Literature

Talaromyces marneffeiMp1 protein, a novel virulence factor, carries two arachidonic acid-binding domains to suppress inflammatory responses in hosts

Lam, W.H.Sze, K.H.Ke, Y.Tse, M.K.Zhang, H.Woo, P.C.Y.Lau, S.K.P.Lau, C.C.Y.Xu, S.Lai, P.M.Zhou, T.Antonyuk, S.V.Kao, R.Y.T.Yuen, K.Y.Hao, Q.

(2019) Infect Immun 

  • DOI: https://doi.org/10.1128/IAI.00679-18
  • Primary Citation of Related Structures:  
    5E7X, 5ECF, 6J6F

  • PubMed Abstract: 

    Talaromyces marneffei infection causes talaromycosis (previously known as penicilliosis), a very important opportunistic systematic mycosis in immunocompromised patients. Different virulence mechanisms in T. marneffei have been proposed and investigated. In the sera of patients with talaromycosis, Mp1 protein (Mp1p), a secretory galactomannoprotein antigen with two tandem ligand-binding domains (Mp1p-LBD1 and Mp1p-LBD2), was found to be abundant. Mp1p-LBD2 was reported to possess a hydrophobic cavity to bind copurified palmitic acid (PLM). It was hypothesized that capturing of lipids from human hosts by expressing a large quantity of Mp1p is a virulence mechanism of T. marneffei It was shown that expression of Mp1p enhanced the intracellular survival of T. marneffei by suppressing proinflammatory responses. Mechanistic study of Mp1p-LBD2 suggested that arachidonic acid (AA), a precursor of paracrine signaling molecules for regulation of inflammatory responses, is the major physiological target of Mp1p-LBD2. In this study, we use crystallographic and biochemical techniques to further demonstrate that Mp1p-LBD1, the previously unsolved first lipid binding domain of Mp1p, is also a strong AA-binding domain in Mp1p. These studies on Mp1p-LBD1 support the idea that the highly expressed Mp1p is an effective AA-capturing protein. Each Mp1p can bind up to 4 AA molecules. The crystal structure of Mp1p-LBD1-LBD2 has also been solved, showing that both LBDs are likely to function independently with a flexible linker between them. T. marneffei and potentially other pathogens highly expressing and secreting proteins similar to Mp1p can severely disturb host signaling cascades during proinflammatory responses by reducing the availabilities of important paracrine signaling molecules.


  • Organizational Affiliation

    School of Biomedical Sciences, 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
Cell wall antigen
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J
151Talaromyces marneffei PM1Mutation(s): 0 
UniProt
Find proteins for A8HBN5 (Talaromyces marneffei)
Explore A8HBN5 
Go to UniProtKB:  A8HBN5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA8HBN5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.256 
  • R-Value Observed: 0.258 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.675α = 90
b = 104.274β = 97.44
c = 108.103γ = 90
Software Package:
Software NamePurpose
DENZOdata collection
SCALEPACKdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-10-19
    Type: Initial release
  • Version 2.0: 2019-03-06
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Experimental preparation, Non-polymer description, Other, Polymer sequence, Refinement description, Source and taxonomy, Structure summary
  • Version 2.1: 2019-04-10
    Changes: Data collection, Database references
  • Version 2.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description