4RI0

Serine Protease HtrA3, mutationally inactivated


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.27 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural and Functional Analysis of Human HtrA3 Protease and Its Subdomains.

Glaza, P.Osipiuk, J.Wenta, T.Zurawa-Janicka, D.Jarzab, M.Lesner, A.Banecki, B.Skorko-Glonek, J.Joachimiak, A.Lipinska, B.

(2015) PLoS One 10: e0131142-e0131142

  • DOI: https://doi.org/10.1371/journal.pone.0131142
  • Primary Citation of Related Structures:  
    4RI0

  • PubMed Abstract: 

    Human HtrA3 protease, which induces mitochondria-mediated apoptosis, can be a tumor suppressor and a potential therapeutic target in the treatment of cancer. However, there is little information about its structure and biochemical properties. HtrA3 is composed of an N-terminal domain not required for proteolytic activity, a central serine protease domain and a C-terminal PDZ domain. HtrA3S, its short natural isoform, lacks the PDZ domain which is substituted by a stretch of 7 C-terminal amino acid residues, unique for this isoform. This paper presents the crystal structure of the HtrA3 protease domain together with the PDZ domain (ΔN-HtrA3), showing that the protein forms a trimer whose protease domains are similar to those of human HtrA1 and HtrA2. The ΔN-HtrA3 PDZ domains are placed in a position intermediate between that in the flat saucer-like HtrA1 SAXS structure and the compact pyramidal HtrA2 X-ray structure. The PDZ domain interacts closely with the LB loop of the protease domain in a way not found in other human HtrAs. ΔN-HtrA3 with the PDZ removed (ΔN-HtrA3-ΔPDZ) and an N-terminally truncated HtrA3S (ΔN-HtrA3S) were fully active at a wide range of temperatures and their substrate affinity was not impaired. This indicates that the PDZ domain is dispensable for HtrA3 activity. As determined by size exclusion chromatography, ΔN-HtrA3 formed stable trimers while both ΔN-HtrA3-ΔPDZ and ΔN-HtrA3S were monomeric. This suggests that the presence of the PDZ domain, unlike in HtrA1 and HtrA2, influences HtrA3 trimer formation. The unique C-terminal sequence of ΔN-HtrA3S appeared to have little effect on activity and oligomerization. Additionally, we examined the cleavage specificity of ΔN-HtrA3. Results reported in this paper provide new insights into the structure and function of ΔN-HtrA3, which seems to have a unique combination of features among human HtrA proteases.


  • Organizational Affiliation

    Department of Biochemistry, Faculty of Biology, University of Gdansk, 80-308 Gdansk, Poland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine protease HTRA3
A, B, C
332Homo sapiensMutation(s): 1 
Gene Names: HTRA3PRSP
EC: 3.4.21
UniProt & NIH Common Fund Data Resources
Find proteins for P83110 (Homo sapiens)
Explore P83110 
Go to UniProtKB:  P83110
PHAROS:  P83110
GTEx:  ENSG00000170801 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP83110
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 118.981α = 90
b = 118.981β = 90
c = 167.86γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
SBC-Collectdata collection
HKL-3000data reduction
HKL-3000data scaling
MOLREPphasing
HKL-3000phasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-29
    Type: Initial release
  • Version 1.1: 2015-09-09
    Changes: Database references
  • Version 1.2: 2017-11-22
    Changes: Refinement description
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description