FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2806805364> ?p ?o ?g. }

• W2806805364 endingPage "11877" @default.
• W2806805364 startingPage "11867" @default.
• W2806805364 abstract "Streptococcus agalactiae is an important human opportunistic pathogen that can cause serious health problems, particularly among newborns and older individuals. S. agalactiae contains the CAMP factor, a pore-forming toxin first identified in this bacterium. The CAMP reaction is based on the co-hemolytic activity of the CAMP factor and is commonly used to identify S. agalactiae in the clinic. Closely related proteins are present also in other Gram-positive pathogens. Although the CAMP toxin was discovered more than a half century ago, no structure from this toxin family has been reported, and the mechanism of action of this toxin remains unclear. Here, we report the first structure of this toxin family, revealing a structural fold composed of 5 + 3-helix bundles. Further analysis by protein truncation and site-directed mutagenesis indicated that the N-terminal 5-helix bundle is responsible for membrane permeabilization, whereas the C-terminal 3-helix bundle is likely responsible for host receptor binding. Interestingly, the C-terminal domain inhibited the activity of both full-length toxin and its N-terminal domain. Moreover, we observed that the linker region is highly conserved and has a conserved DLXXXDXAT sequence motif. Structurally, this linker region extensively interacted with both terminal CAMP factor domains, and mutagenesis disclosed that the conserved sequence motif is required for CAMP factor's co-hemolytic activity. In conclusion, our results reveal a unique structure of this bacterial toxin and help clarify the molecular mechanism of its co-hemolytic activity. Streptococcus agalactiae is an important human opportunistic pathogen that can cause serious health problems, particularly among newborns and older individuals. S. agalactiae contains the CAMP factor, a pore-forming toxin first identified in this bacterium. The CAMP reaction is based on the co-hemolytic activity of the CAMP factor and is commonly used to identify S. agalactiae in the clinic. Closely related proteins are present also in other Gram-positive pathogens. Although the CAMP toxin was discovered more than a half century ago, no structure from this toxin family has been reported, and the mechanism of action of this toxin remains unclear. Here, we report the first structure of this toxin family, revealing a structural fold composed of 5 + 3-helix bundles. Further analysis by protein truncation and site-directed mutagenesis indicated that the N-terminal 5-helix bundle is responsible for membrane permeabilization, whereas the C-terminal 3-helix bundle is likely responsible for host receptor binding. Interestingly, the C-terminal domain inhibited the activity of both full-length toxin and its N-terminal domain. Moreover, we observed that the linker region is highly conserved and has a conserved DLXXXDXAT sequence motif. Structurally, this linker region extensively interacted with both terminal CAMP factor domains, and mutagenesis disclosed that the conserved sequence motif is required for CAMP factor's co-hemolytic activity. In conclusion, our results reveal a unique structure of this bacterial toxin and help clarify the molecular mechanism of its co-hemolytic activity." @default.
• W2806805364 created "2018-06-13" @default.
• W2806805364 creator A5002790683 @default.
• W2806805364 creator A5014165464 @default.
• W2806805364 creator A5038549808 @default.
• W2806805364 creator A5042300878 @default.
• W2806805364 creator A5043670602 @default.
• W2806805364 creator A5077782538 @default.
• W2806805364 creator A5087214271 @default.
• W2806805364 date "2018-07-01" @default.
• W2806805364 modified "2023-10-18" @default.
• W2806805364 title "Crystal structure of the Streptococcus agalactiae CAMP factor provides insights into its membrane-permeabilizing activity" @default.
• W2806805364 cites W1539796472 @default.
• W2806805364 cites W1955736963 @default.
• W2806805364 cites W1965910641 @default.
• W2806805364 cites W1970476189 @default.
• W2806805364 cites W1972513271 @default.
• W2806805364 cites W1978007992 @default.
• W2806805364 cites W1987268593 @default.
• W2806805364 cites W1994342014 @default.
• W2806805364 cites W1995816419 @default.
• W2806805364 cites W1998490996 @default.
• W2806805364 cites W2000471751 @default.
• W2806805364 cites W2001276190 @default.
• W2806805364 cites W2004377868 @default.
• W2806805364 cites W2005785414 @default.
• W2806805364 cites W2005986251 @default.
• W2806805364 cites W2006804081 @default.
• W2806805364 cites W2012531419 @default.
• W2806805364 cites W2017964099 @default.
• W2806805364 cites W2019065665 @default.
• W2806805364 cites W2019234618 @default.
• W2806805364 cites W2019786774 @default.
• W2806805364 cites W2030517878 @default.
• W2806805364 cites W2030683115 @default.
• W2806805364 cites W2048769804 @default.
• W2806805364 cites W2050119515 @default.
• W2806805364 cites W2051146598 @default.
• W2806805364 cites W2067042270 @default.
• W2806805364 cites W2073561387 @default.
• W2806805364 cites W2097632784 @default.
• W2806805364 cites W2097676480 @default.
• W2806805364 cites W2102506381 @default.
• W2806805364 cites W2114930488 @default.
• W2806805364 cites W2117995237 @default.
• W2806805364 cites W2122540662 @default.
• W2806805364 cites W2128653811 @default.
• W2806805364 cites W2132763224 @default.
• W2806805364 cites W2142713529 @default.
• W2806805364 cites W2144081223 @default.
• W2806805364 cites W2144998676 @default.
• W2806805364 cites W2147874841 @default.
• W2806805364 cites W2151678109 @default.
• W2806805364 cites W2151940437 @default.
• W2806805364 cites W2153949626 @default.
• W2806805364 cites W2154714625 @default.
• W2806805364 cites W2163341755 @default.
• W2806805364 cites W2164350157 @default.
• W2806805364 cites W2170116275 @default.
• W2806805364 cites W2177299352 @default.
• W2806805364 cites W2181395626 @default.
• W2806805364 cites W2195753589 @default.
• W2806805364 cites W2516689178 @default.
• W2806805364 cites W2582045181 @default.
• W2806805364 cites W2602465944 @default.
• W2806805364 cites W2616649382 @default.
• W2806805364 doi "https://doi.org/10.1074/jbc.ra118.002336" @default.
• W2806805364 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6066297" @default.
• W2806805364 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29884770" @default.
• W2806805364 hasPublicationYear "2018" @default.
• W2806805364 type Work @default.
• W2806805364 sameAs 2806805364 @default.
• W2806805364 citedByCount "13" @default.
• W2806805364 countsByYear W28068053642019 @default.
• W2806805364 countsByYear W28068053642020 @default.
• W2806805364 countsByYear W28068053642021 @default.
• W2806805364 countsByYear W28068053642022 @default.
• W2806805364 countsByYear W28068053642023 @default.
• W2806805364 crossrefType "journal-article" @default.
• W2806805364 hasAuthorship W2806805364A5002790683 @default.
• W2806805364 hasAuthorship W2806805364A5014165464 @default.
• W2806805364 hasAuthorship W2806805364A5038549808 @default.
• W2806805364 hasAuthorship W2806805364A5042300878 @default.
• W2806805364 hasAuthorship W2806805364A5043670602 @default.
• W2806805364 hasAuthorship W2806805364A5077782538 @default.
• W2806805364 hasAuthorship W2806805364A5087214271 @default.
• W2806805364 hasBestOaLocation W28068053641 @default.
• W2806805364 hasConcept C104317684 @default.
• W2806805364 hasConcept C111919701 @default.
• W2806805364 hasConcept C117745874 @default.
• W2806805364 hasConcept C132677234 @default.
• W2806805364 hasConcept C16318435 @default.
• W2806805364 hasConcept C167625842 @default.
• W2806805364 hasConcept C174921431 @default.
• W2806805364 hasConcept C2776460866 @default.
• W2806805364 hasConcept C2777367657 @default.
• W2806805364 hasConcept C2777860557 @default.
• W2806805364 hasConcept C2778276568 @default.

• next