G14secL04Tpc3: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
|||
| Line 8: | Line 8: | ||
===Outer Surface Proteins=== | ===Outer Surface Proteins=== | ||
Colonization and survival of ''Borrelia burgdorferi'' within ticks and mammals is facilitated, in part, by [http://en.wikipedia.org/wiki/Lipoprotein lipoproteins]. OspB and OspA are two of the major lipoproteins present on the outer surface of the spirochete Borrelia Burgdoferi. Studies have shown that OspB is critical for the adherence of the spirochete to the gut wall of its tick vector. The free OspB structure consists of a barrel domain which might be the portion that interacts with a protein or a linear saccharide in the tick-gut, promoting the attachment of spirochete on the tick gut. It’s speculated that destroying these lipoproteins will cause bacterial death of spirochetes. Some antibody Fab fragments such as H6831 and CB2 have been shown to cause bacterial lysis of spirochetes by binding to these lipoproteins in the absence of phagocytes and without [http://en.wikipedia.org/wiki/Complement_system complement], which is normally part of the immune response to bacteria. However, it remains unclear how binding of H6831 or CB2 can lead directly to lysis of the bacterium. | Colonization and survival of ''Borrelia burgdorferi'' within ticks and mammals is facilitated, in part, by [http://en.wikipedia.org/wiki/Lipoprotein lipoproteins]. OspB and OspA are two of the major lipoproteins present on the outer surface of the spirochete Borrelia Burgdoferi. Studies have shown that OspB is critical for the adherence of the spirochete to the gut wall of its tick vector. The free OspB structure consists of a barrel domain which might be the portion that interacts with a protein or a linear saccharide in the tick-gut, promoting the attachment of spirochete on the tick gut<ref name="1rjl_pdb">http://www.jbc.org/content/280/17/17363.full</ref>. It’s speculated that destroying these lipoproteins will cause bacterial death of spirochetes. Some antibody Fab fragments such as H6831 and CB2 have been shown to cause bacterial lysis of spirochetes by binding to these lipoproteins in the absence of phagocytes and without [http://en.wikipedia.org/wiki/Complement_system complement], which is normally part of the immune response to bacteria<ref name ="1rjl_pdb" />. However, it remains unclear how binding of H6831 or CB2 can lead directly to lysis of the bacterium. | ||
===Transmission of Spirochete=== | ===Transmission of Spirochete=== | ||
| Line 22: | Line 22: | ||
form two sheets that bend, along with the final <scene name='G14secL04Tpc3/8-12_beta_strands_showing/2'>alpha-helix</scene> | form two sheets that bend, along with the final <scene name='G14secL04Tpc3/8-12_beta_strands_showing/2'>alpha-helix</scene> | ||
that comes over the top into the <scene name='G14secL04Tpc3/C-terminal_barrel_domain/4'>C-terminal barrel domain </scene> | that comes over the top into the <scene name='G14secL04Tpc3/C-terminal_barrel_domain/4'>C-terminal barrel domain </scene> | ||
. It has been shown that OspB deficient spirochetes lack the ability to bind to the tick gut<ref> http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0030033</ref>. Further studies suggest that the structural barrel domain is what gives OspB the ability to adhere to the tick gut wall. The barrel domain cavity could serve as the binding site for an exposed protein loop, small peptide, or linear saccharide hanging off the tick gut wall<ref name="1rjl_pdb" | . It has been shown that OspB deficient spirochetes lack the ability to bind to the tick gut<ref> http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0030033</ref>. Further studies suggest that the structural barrel domain is what gives OspB the ability to adhere to the tick gut wall. The barrel domain cavity could serve as the binding site for an exposed protein loop, small peptide, or linear saccharide hanging off the tick gut wall<ref name="1rjl_pdb" />. <scene name='G14secL04Tpc3/1-4_beta_strands_showing/1'>Beta strands 1-4 </scene> on free OspB's N-terminus are cleaved when OspB is bound to antibody fragment H6831, suggesting that they're removed by the proteolysis in the H6831-bound complex<ref name = "1rjl_pdb" />. The OspB protein is an integral membrane lipoprotein, with its lipidated N-terminus imbedded in the outer membrane of the spirochete and its C-terminus directed away from the membrane<ref>http://iai.asm.org/content/58/4/983.short</ref>. Therefore, it is speculated that proteolytic action on these N-terminus beta strands somehow cause lysis of the spirochete. Studies have shown that when complement-independent antibodies such as H6831 act on OspB, the result is blebbing of the outer membrane of the bacteria <ref name="Blebbing">http://www.jstor.org/stable/40483625?&Search=yes&searchText=region&searchText=antibody&searchText=protein&searchText=directed&searchText=bactericidal&searchText=Borrelia&searchText=variable&searchText=burgdorferi&searchText=OspB&list=hide&searchUri=%2Faction%2FdoBasicSearch%3FQuery%3D%2BA%2Bbactericidal%2Bantibody%2Bto%2BBorrelia%2Bburgdorferi%2Bis%2Bdirected%2Bagainst%2Ba%2Bvariable%2Bregion%2Bof%2Bthe%2BOspB%2Bprotein%26acc%3Don%26wc%3Don&prevSearch=&item=3&ttl=7&returnArticleService=showFullText</ref>. This blebbing of the bacterial membrane has been shown to create small openings in the outer membrane of the bacteria, which leads for potential osmotic lysis depending on the solution the bacteria is in<ref name="Blebbing" />. | ||
