Streptococcus pneumoniae IgA1 protease: A metalloprotease that can catalyze in a split manner in vitro

IgA1 proteases (IgA1P) from diverse pathogenic bacteria specifically cleave human immunoglobulin A1 (IgA1) at the hinge region, thereby thwarting protective host immune responses. Streptococcus pneumoniae (S. pneumoniae) IgA1P shares no sequence conservation with serine or cysteine types of IgA1Ps o...

Full description

Saved in:
Bibliographic Details
Published in:Protein science 2017-03, Vol.26 (3), p.600-610
Main Authors: Chi, Ying‐Chih, Rahkola, Jeremy T., Kendrick, Agnieszka A., Holliday, Michael J., Paukovich, Natasia, Roberts, Thomas S., Janoff, Edward N., Eisenmesser, Elan Z.
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Architecture
Bacteria
Bacterial Proteins - chemistry
Binding
Catalysis
Cell surface
Conserved sequence
IgA1 protease
Immune response
metalloprotease
Metalloproteinase
Penicillin
protease turnover
Protein Domains
Proteins
Serine
Serine Endopeptidases - chemistry
split protease
streptococcal pneumoniae
Streptococcus infections
Streptococcus pneumoniae
Streptococcus pneumoniae - enzymology
Virulence
Virulence factors
Virulence Factors - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:IgA1 proteases (IgA1P) from diverse pathogenic bacteria specifically cleave human immunoglobulin A1 (IgA1) at the hinge region, thereby thwarting protective host immune responses. Streptococcus pneumoniae (S. pneumoniae) IgA1P shares no sequence conservation with serine or cysteine types of IgA1Ps or other known proteins, other than a conserved HExxH Zn‐binding motif (1604‐1608) found in metalloproteases. We have developed a novel expression system to produce the mature S. pneumoniae IgA1P and we have discovered that this form is both attached to the bacterial cell surface and released in its full form. Our data demonstrate that the S. pneumoniae IgA1P comprises two distinct regions that associate to form an active metalloprotease, the first such example of a metalloprotease that can be split in vitro and recombined to form an active enzyme. By capitalizing on this novel domain architecture, we show that the N‐terminal region of S. pneumoniae IgA1P comprises the primary binding region for IgA1, although the C‐terminal region of S. pneumoniae IgA1P is necessary for cleavage of IgA1. Our findings lend insight into the protein domain architecture of the S. pneumoniae IgA1P and function of this important virulence factor for S. pneumoniae infection.
ISSN:0961-8368
1469-896X
DOI:10.1002/pro.3110