title: The flexible loop of Staphylococcus aureus IsdG is required for its degradation in the absence of heme.
abstract: Degradation of specific native proteins allows bacteria to rapidly adapt to changing environments when the activity of those proteins is no longer required. Although these processes are vital to bacterial survival, relatively little is known regarding how bacterial proteins are recognized and targeted for degradation. Staphylococcus aureus is an important human pathogen that requires iron for growth and pathogenesis. In the vertebrate host, S. aureus fulfills its iron requirement by obtaining heme iron from host hemoproteins via IsdG- and IsdI-mediated heme degradation. IsdG and IsdI are structurally and mechanistically analogous but are differentially regulated by iron and heme availability. Specifically, IsdG is targeted for degradation in the absence of heme. Therefore, we utilized the differential regulation of IsdG and IsdI to investigate the mechanism of regulated proteolysis. In contrast to canonical protease recognition sequences, we show that IsdG is targeted for degradation by internally coded sequences. Specifically, a flexible loop near the heme-binding pocket is required for IsdG degradation in the absence of heme.
authors: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors: Michelle L
authors: ML
authors: Reniere
authors: Kathryn P
authors: KP
authors: Haley
authors: Eric P
authors: EP
authors: Skaar
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018390:Gene Targeting; D006418:Heme / Q000172:deficiency* / Q000235:genetics; D006420:Hemeproteins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050506:Mutant Chimeric Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010105:Oxygenases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D011487:Protein Conformation; D011489:Protein Denaturation; D055550:Protein Stability; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D006420:Hemeproteins; D050506:Mutant Chimeric Proteins; D006418:Heme; D007501:Iron; C497164:IsdI protein, Staphylococcus aureus; D006899:Mixed Function Oxygenases; D010105:Oxygenases; C482079:IsdG protein, Staphylococcus aureus