title: Streptococcus pneumoniae IgA1 protease: A metalloprotease that can catalyze in a split manner in vitro.
abstract: 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.
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO.
authors.forename: Ying-Chih
authors.initials: YC
authors.lastname: Chi
authors.affiliation: Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, CO.|Denver Veterans Affairs Medical Center, Denver, CO.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Rahkola
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Kendrick
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holliday
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO.
authors.forename: Natasia
authors.initials: N
authors.lastname: Paukovich
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Roberts
authors.affiliation: Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, CO.|Denver Veterans Affairs Medical Center, Denver, CO.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Janoff
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO.
authors.forename: Elan Z
authors.initials: EZ
authors.lastname: Eisenmesser
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry*; D002384:Catalysis; D000072417:Protein Domains; D012697:Serine Endopeptidases / Q000737:chemistry*; D013296:Streptococcus pneumoniae / Q000201:enzymology*; D037521:Virulence Factors / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase
keywords: IgA1 protease; metalloprotease; protease turnover; split protease; streptococcal pneumoniae