G14secL04Tpc3: Difference between revisions
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<Structure load='1rjl' size='350' frame='true' align='right' caption= 'OspB bound to H6831' scene= 'G14secL04Tpc3/Ospb_in_complex/2'/> | <Structure load='1rjl' size='350' frame='true' align='right' caption= 'OspB bound to H6831' scene= 'G14secL04Tpc3/Ospb_in_complex/2'/> | ||
<scene name='G14secL04Tpc3/Antibody_showing2/1'>Antibody Fab fragment H6831 </scene> (<scene name='G14secL04Tpc3/Heavy_chain/1'>Heavy chain</scene> and <scene name='G14secL04Tpc3/Light_chain/1'>light chain</scene>)has been shown to bind on an epitope of the <scene name='G14secL04Tpc3/Ospb_in_complex_with_heavy_and/2'>OspB protein</scene><ref name ="1rjl_pdb" />. Once this occurs, the resulting OspB∙H6831 complex is formed and the first four beta strands of the OspB protein are proteolysed<ref name ="1rjl_pdb" />. Cleavage of these first four beta strands somehow causes bacterial lysis of the ''B. burdgorferi''. This loss is the most significant conformational change in the OspB protein itself, and all other changes are minor and appear to be related to this loss. The majority of the binding occurs on the C-terminus of OspB. The C-terminus consists of <scene name='G14secL04Tpc3/Three_major_loops2/ | <scene name='G14secL04Tpc3/Antibody_showing2/1'>Antibody Fab fragment H6831 </scene> (<scene name='G14secL04Tpc3/Heavy_chain/1'>Heavy chain</scene> and <scene name='G14secL04Tpc3/Light_chain/1'>light chain</scene>)has been shown to bind on an epitope of the <scene name='G14secL04Tpc3/Ospb_in_complex_with_heavy_and/2'>OspB protein</scene><ref name ="1rjl_pdb" />. Once this occurs, the resulting OspB∙H6831 complex is formed and the first four beta strands of the OspB protein are proteolysed<ref name ="1rjl_pdb" />. Cleavage of these first four beta strands somehow causes bacterial lysis of the ''B. burdgorferi''. This loss is the most significant conformational change in the OspB protein itself, and all other changes are minor and appear to be related to this loss. The majority of the binding occurs on the C-terminus of OspB. The C-terminus consists of <scene name='G14secL04Tpc3/Three_major_loops2/4'>three major loops </scene> | ||
that are involved in the electrostatic forces keeping the H6831 antibody bound to the OspB protein<ref name ="1rjl_pdb" />. Of these three loops, <scene name='G14secL04Tpc3/Loop_2/4'>loop | that are involved in the electrostatic forces keeping the H6831 antibody bound to the OspB protein<ref name ="1rjl_pdb" />. Of these three loops, <scene name='G14secL04Tpc3/Loop_2/4'>the middle loop </scene> | ||
plays the most significant role in keeping the complex together. This is due to the presence of a <scene name='G14secL04Tpc3/Lysine-253/3'>lysine at residue 253</scene> | plays the most significant role in keeping the complex together. This is due to the presence of a <scene name='G14secL04Tpc3/Lysine-253/3'>lysine at residue 253</scene> | ||
on this loop. This important lysine forms an ionic salt bridge with the <scene name='G14secL04Tpc3/Lysine-253_and_glu50/2'>glutamic acid at residue 50</scene> | on this loop. This important lysine forms an ionic salt bridge with the <scene name='G14secL04Tpc3/Lysine-253_and_glu50/2'>glutamic acid at residue 50</scene> | ||
on the heavy chain of the antibody Fab Fragment. Thus, formation of the complex consist of the C-terminus of the OspB protein coming into contact with the variable regions of the H6831 antibody Fab fragment and the lysine-253 wedging between the two <scene name='G14secL04Tpc3/Lysine-253_glu50_tyr_and_trp/2'>aromatic residues</scene> | on the heavy chain of the antibody Fab Fragment. Thus, formation of the complex consist of the C-terminus of the OspB protein coming into contact with the variable regions of the H6831 antibody Fab fragment and the lysine-253 wedging between the two <scene name='G14secL04Tpc3/Lysine-253_glu50_tyr_and_trp/2'>aromatic residues</scene> | ||
(tryptophan-33 and tyrosine-101) and salt bridging with the glu-50 on the heavy chain of the antibody<ref name ="1rjl_pdb" />. Studies show that other bacterial strains having a cysteine, glycine, glutamic acid, or threonine in place of Lys-253 demonstrate resistance to the bactericidal effects of H6831 and also less binding affinity for the antibody Fab fragment <ref>A Sadziene, M Jonsson, S Bergström, R K Bright, R C Kennedy and A G Barbour. Infect. Immun. 1994, 62(5):2037. http://iai.asm.org/content/62/5/2037.short</ref>. This bolsters how important the Lys-253 is in the binding between the OspB protein and the antibody. Additionally, one report found that an ospB escape mutant in a population of infectious ''B. burgdorferi'', with a single base change in the ribosomal binding sequence and a single nucleotide deletion in the open reading frame of the ospB gene, demonstrated reduced expression and truncation of the OspB protein<ref name ="30_Sadziene"> A Sadziene, A G Barbour, P A Rosa and D D Thomas. Infect. Immun. 1993, 61(9):3590. http://iai.asm.org/content/61/9/3590.short</ref>. This reduced expression and truncation of OspB extenuated the penetration capability and infectivity of the spirochete in the human umbilical vein endothelium cells<ref name = "30_Sadziene" />. Thus, the OspB protein plays a fairly important role in the ability of the spirochete to infect a host. After the complex is formed and the first four beta strands are cleaved off, a relic of this loss is a single <scene name='G14secL04Tpc3/Freely_floating_beta_strand/2'>freely floating beta strand</scene> on the N-terminus of the protein. This beta strand plays a role in the formation of dimers of OspB∙H6831 complex <ref name="1rjl_pdb" /> . Although the | (tryptophan-33 and tyrosine-101) and salt bridging with the glu-50 on the heavy chain of the antibody<ref name ="1rjl_pdb" />. Studies show that other bacterial strains having a cysteine, glycine, glutamic acid, or threonine in place of Lys-253 demonstrate resistance to the bactericidal effects of H6831 and also less binding affinity for the antibody Fab fragment <ref>A Sadziene, M Jonsson, S Bergström, R K Bright, R C Kennedy and A G Barbour. Infect. Immun. 1994, 62(5):2037. http://iai.asm.org/content/62/5/2037.short</ref>. This bolsters how important the Lys-253 is in the binding between the OspB protein and the antibody. Additionally, one report found that an ospB escape mutant in a population of infectious ''B. burgdorferi'', with a single base change in the ribosomal binding sequence and a single nucleotide deletion in the open reading frame of the ospB gene, demonstrated reduced expression and truncation of the OspB protein<ref name ="30_Sadziene"> A Sadziene, A G Barbour, P A Rosa and D D Thomas. Infect. Immun. 1993, 61(9):3590. http://iai.asm.org/content/61/9/3590.short</ref>. This reduced expression and truncation of OspB extenuated the penetration capability and infectivity of the spirochete in the human umbilical vein endothelium cells<ref name = "30_Sadziene" />. Thus, the OspB protein plays a fairly important role in the ability of the spirochete to infect a host. After the complex is formed and the first four beta strands are cleaved off, a relic of this loss is a single <scene name='G14secL04Tpc3/Freely_floating_beta_strand/2'>freely floating beta strand</scene> on the N-terminus of the protein. This beta strand plays a role in the formation of dimers of OspB∙H6831 complex <ref name="1rjl_pdb" /> . Although the middle loop bearing the lysine is very important, the other loops certainly contribute to the bonding between OspB and the antibody fab fragment. For example, a <scene name='G14secL04Tpc3/Threonine_and_light_chain/1'>threonine</scene> | ||
at residue 276 on another loop interacts with residues on the light chain of the antibody fragment. | at residue 276 on another loop interacts with residues on the light chain of the antibody fragment. | ||
