Sandbox Reserved 1771: Difference between revisions

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==Structure==

Exploring the different sections of a BCR, the antigen binding site (located in the extracellular region) is specific to antigens, but the process is highly conserved across different BCRs. More specifically, the IgM BCR has a unique interaction concerning its Fc chains and a/b subunits. These interactions contribute to the overall structure of the protein. Within the a/b subunits themselves, there are several intermolecular interactions that cause the subunits to remain associated with each other. The following section explores these different domains and interactions in more detail.

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===Fc and α/β Interactions===

While the antigen binding site structure of the mIgM BCR is identical to other common soluble antibodies, there are several intracellular interactions between the heavy chains and Igα/β subunits that make it unique. In the Fc portion of the structure, the two heavy chains interact via a disulfide bond and form an <scene name='95/952700/O-shaped_ring/3'>O-shaped ring</scene>. Additionally, the Fc portion binds the <scene name='95/952700/O-shaped_ring/2'>Ig α/β heterodimer</scene> with 1:1 stoichiometry. <Ref name="Tolar P"> Tolar P, Pierce SK. Unveiling the B cell receptor structure. Science. 2022 Aug 19;377(6608):819-820. [doi: 10.1126/science.add8065. Epub 2022 Aug 18. PMID: 35981020.] </Ref>. Due to the orientation of the heavy chains in the O-shaped ring, only Heavy chain 1 (Hc1) forms direct interactions with the Igα/β heterodimer. Furthermore, <scene name='95/952700/Ig-a_and_hc_1/4'>Hc1 and Igα interact</scene> through two hydrogen bonds (T75-Q487 and N73-Q493) which are stabilized by sandwiching of aromatic residues (W76 sandwiched between F358 and F485). Similarly, <scene name='95/952700/Igb_and_hc/1'>Hc1 and Igβ interact</scene> through three hydrogen bonds (Y66-R491, K62-T530, and R55-T533,). The residues involved in the interactions at the heavy chain and Igα/β interface are highly conserved across all species, suggesting a conserved mode of interaction. <Ref name="Su Q"> Su Q, Chen M, Shi Y, Zhang X, Huang G, Huang B, Liu D, Liu Z, Shi Y. Cryo-EM structure of the human IgM B cell receptor. Science. 2022 Aug 19;377(6608):875-880. [doi: 10.1126/science.abo3923. Epub 2022 Aug 18. PMID: 35981043.]</Ref>. The Igα/β heterodimer is an obligate component of all BCRs. Igα and Igβ non-covalently associate with mIgM, and are crucial components for initiating biochemical signaling inside the B cell upon antigen binding. <Ref name="Tolar P"> Tolar P, Pierce SK. Unveiling the B cell receptor structure. Science. 2022 Aug 19;377(6608):819-820. [doi: 10.1126/science.add8065. Epub 2022 Aug 18. PMID: 35981020.] </Ref>. <scene name='95/952700/Iga_and_igb/1'>Igα and Igβ are associated</scene> by a disulfide bond between ~~cystine~~ residues (C119-C136). The disulfide bond is stabilized by π-π stacking (Y122 and F52) and a hydrogen bond (G120-R51). These residues are highly conserved across species, suggesting conservation of the Igα/β interface.

While the antigen binding site structure of the mIgM BCR is identical to other common soluble antibodies, there are several intracellular interactions between the heavy chains and Igα/β subunits that make it unique. In the Fc portion of the structure, the two heavy chains interact via a disulfide bond and form an <scene name='95/952700/O-shaped_ring/3'>O-shaped ring</scene>. Additionally, the Fc portion binds the <scene name='95/952700/O-shaped_ring/2'>Ig α/β heterodimer</scene> with 1:1 stoichiometry. <Ref name="Tolar P"> Tolar P, Pierce SK. Unveiling the B cell receptor structure. Science. 2022 Aug 19;377(6608):819-820. [doi: 10.1126/science.add8065. Epub 2022 Aug 18. PMID: 35981020.] </Ref>. Due to the orientation of the heavy chains in the O-shaped ring, only Heavy chain 1 (Hc1) forms direct interactions with the Igα/β heterodimer. Furthermore, <scene name='95/952700/Ig-a_and_hc_1/4'>Hc1 and Igα interact</scene> through two hydrogen bonds (T75-Q487 and N73-Q493) which are stabilized by sandwiching of aromatic residues (W76 sandwiched between F358 and F485). Similarly, <scene name='95/952700/Igb_and_hc/1'>Hc1 and Igβ interact</scene> through three hydrogen bonds (Y66-R491, K62-T530, and R55-T533,). The residues involved in the interactions at the heavy chain and Igα/β interface are highly conserved across all species, suggesting a conserved mode of interaction. <Ref name="Su Q"> Su Q, Chen M, Shi Y, Zhang X, Huang G, Huang B, Liu D, Liu Z, Shi Y. Cryo-EM structure of the human IgM B cell receptor. Science. 2022 Aug 19;377(6608):875-880. [doi: 10.1126/science.abo3923. Epub 2022 Aug 18. PMID: 35981043.]</Ref>. The Igα/β heterodimer is an obligate component of all BCRs. Igα and Igβ non-covalently associate with mIgM, and are crucial components for initiating biochemical signaling inside the B cell upon antigen binding. <Ref name="Tolar P"> Tolar P, Pierce SK. Unveiling the B cell receptor structure. Science. 2022 Aug 19;377(6608):819-820. [doi: 10.1126/science.add8065. Epub 2022 Aug 18. PMID: 35981020.] </Ref>. <scene name='95/952700/Iga_and_igb/1'>Igα and Igβ are associated</scene> by a disulfide bond between cysteine residues (C119-C136). The disulfide bond is stabilized by π-π stacking (Y122 and F52) and a hydrogen bond (G120-R51). These residues are highly conserved across species, suggesting conservation of the Igα/β interface.

===Transmembrane Interactions===

Many transmembrane interactions can be found within a IgM B-cell receptor. The <scene name='95/952699/Transmembrane_region/1'>α and β subunits</scene> have numerous interactions that keep them associated with each other. An overview of all residue interactions can be found <scene name='95/952699/Overview_hbonds_fixed/1'>here</scene> (highlighted in green). At a cellular pH, various amino acid residues found in the transmembrane region are charged as well, which strengthens the overall interaction. For example, <scene name='95/952699/N155_e138_hbonds_fixed/1'>a hydrogen bond</scene> between residues N155 and E138, along with numerous other hydrogen bonds, works to stabilize the α-β chain interactions. Further down the chains, <scene name='95/952699/T166_e148_hbonds_fixed/1'>interactions</scene> between residues T166 and E148 also have strong hydrogen bonding. Overall, these hydrogen bonds and ion interactions work to maintain the association of the α-β chains.

Many transmembrane interactions can be found within a IgM B-cell receptor. The <scene name='95/952699/Transmembrane_region/1'>α and β subunits</scene> have numerous interactions that keep them associated with each other. An overview of all residue interactions can be found <scene name='95/952699/Overview_hbonds_fixed/2'>here</scene> (highlighted in green). At a cellular pH, various amino acid residues found in the transmembrane region are charged as well, which strengthens the overall interaction. For example, <scene name='95/952699/N155_e138_hbonds_fixed/2'>a hydrogen bond</scene> between residues N155 and E138, along with numerous other hydrogen bonds, works to stabilize the α-β chain interactions. Further down the chains, <scene name='95/952699/T166_e148_hbonds_fixed/2'>interactions</scene> between residues T166 and E148 also have strong hydrogen bonding. Overall, these hydrogen bonds and ion interactions work to maintain the association of the α-β chains.

</StructureSection>

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@@ Line 6: / Line 6: @@
 ==Structure==
+Exploring the different sections of a BCR, the antigen binding site (located in the extracellular region) is specific to antigens, but the process is highly conserved across different BCRs. More specifically, the IgM BCR has a unique interaction concerning its Fc chains and a/b subunits. These interactions contribute to the overall structure of the protein. Within the a/b subunits themselves, there are several intermolecular interactions that cause the subunits to remain associated with each other. The following section explores these different domains and interactions in more detail.
 <StructureSection load='4INS' size='350' side='right' caption='Human IgM B-Cell Receptor, 7XQ8 (edited)' scene='95/952699/Overview_spin/1'>
@@ Line 13: / Line 14: @@
 ===Fc and α/β Interactions===
-While the antigen binding site structure of the mIgM BCR is identical to other common soluble antibodies, there are several intracellular interactions between the heavy chains and Igα/β subunits that make it unique. In the Fc portion of the structure, the two heavy chains interact via a disulfide bond and form an <scene name='95/952700/O-shaped_ring/3'>O-shaped ring</scene>. Additionally, the Fc portion binds the <scene name='95/952700/O-shaped_ring/2'>Ig α/β heterodimer</scene> with 1:1 stoichiometry. <Ref name="Tolar P"> Tolar P, Pierce SK. Unveiling the B cell receptor structure. Science. 2022 Aug 19;377(6608):819-820. [doi: 10.1126/science.add8065. Epub 2022 Aug 18. PMID: 35981020.] </Ref>. Due to the orientation of the heavy chains in the O-shaped ring, only Heavy chain 1 (Hc1) forms direct interactions with the Igα/β heterodimer. Furthermore, <scene name='95/952700/Ig-a_and_hc_1/4'>Hc1 and Igα interact</scene> through two hydrogen bonds (T75-Q487 and N73-Q493) which are stabilized by sandwiching of aromatic residues (W76 sandwiched between F358 and F485). Similarly, <scene name='95/952700/Igb_and_hc/1'>Hc1 and Igβ interact</scene> through three hydrogen bonds (Y66-R491, K62-T530, and R55-T533,). The residues involved in the interactions at the heavy chain and Igα/β interface are highly conserved across all species, suggesting a conserved mode of interaction. <Ref name="Su Q"> Su Q, Chen M, Shi Y, Zhang X, Huang G, Huang B, Liu D, Liu Z, Shi Y. Cryo-EM structure of the human IgM B cell receptor. Science. 2022 Aug 19;377(6608):875-880. [doi: 10.1126/science.abo3923. Epub 2022 Aug 18. PMID: 35981043.]</Ref>.  The Igα/β heterodimer is an obligate component of all BCRs. Igα and Igβ non-covalently associate with mIgM, and are crucial components for initiating biochemical signaling inside the B cell upon antigen binding. <Ref name="Tolar P"> Tolar P, Pierce SK. Unveiling the B cell receptor structure. Science. 2022 Aug 19;377(6608):819-820. [doi: 10.1126/science.add8065. Epub 2022 Aug 18. PMID: 35981020.] </Ref>. <scene name='95/952700/Iga_and_igb/1'>Igα and Igβ are associated</scene> by a disulfide bond between cystine residues (C119-C136). The disulfide bond is stabilized by π-π stacking (Y122 and F52) and a hydrogen bond (G120-R51). These residues are highly conserved across species, suggesting conservation of the Igα/β interface.
+While the antigen binding site structure of the mIgM BCR is identical to other common soluble antibodies, there are several intracellular interactions between the heavy chains and Igα/β subunits that make it unique. In the Fc portion of the structure, the two heavy chains interact via a disulfide bond and form an <scene name='95/952700/O-shaped_ring/3'>O-shaped ring</scene>. Additionally, the Fc portion binds the <scene name='95/952700/O-shaped_ring/2'>Ig α/β heterodimer</scene> with 1:1 stoichiometry. <Ref name="Tolar P"> Tolar P, Pierce SK. Unveiling the B cell receptor structure. Science. 2022 Aug 19;377(6608):819-820. [doi: 10.1126/science.add8065. Epub 2022 Aug 18. PMID: 35981020.] </Ref>. Due to the orientation of the heavy chains in the O-shaped ring, only Heavy chain 1 (Hc1) forms direct interactions with the Igα/β heterodimer. Furthermore, <scene name='95/952700/Ig-a_and_hc_1/4'>Hc1 and Igα interact</scene> through two hydrogen bonds (T75-Q487 and N73-Q493) which are stabilized by sandwiching of aromatic residues (W76 sandwiched between F358 and F485). Similarly, <scene name='95/952700/Igb_and_hc/1'>Hc1 and Igβ interact</scene> through three hydrogen bonds (Y66-R491, K62-T530, and R55-T533,). The residues involved in the interactions at the heavy chain and Igα/β interface are highly conserved across all species, suggesting a conserved mode of interaction. <Ref name="Su Q"> Su Q, Chen M, Shi Y, Zhang X, Huang G, Huang B, Liu D, Liu Z, Shi Y. Cryo-EM structure of the human IgM B cell receptor. Science. 2022 Aug 19;377(6608):875-880. [doi: 10.1126/science.abo3923. Epub 2022 Aug 18. PMID: 35981043.]</Ref>.  The Igα/β heterodimer is an obligate component of all BCRs. Igα and Igβ non-covalently associate with mIgM, and are crucial components for initiating biochemical signaling inside the B cell upon antigen binding. <Ref name="Tolar P"> Tolar P, Pierce SK. Unveiling the B cell receptor structure. Science. 2022 Aug 19;377(6608):819-820. [doi: 10.1126/science.add8065. Epub 2022 Aug 18. PMID: 35981020.] </Ref>. <scene name='95/952700/Iga_and_igb/1'>Igα and Igβ are associated</scene> by a disulfide bond between cysteine residues (C119-C136). The disulfide bond is stabilized by π-π stacking (Y122 and F52) and a hydrogen bond (G120-R51). These residues are highly conserved across species, suggesting conservation of the Igα/β interface.
 ===Transmembrane Interactions===
-Many transmembrane interactions can be found within a IgM B-cell receptor. The <scene name='95/952699/Transmembrane_region/1'>α and β subunits</scene> have numerous interactions that keep them associated with each other. An overview of all residue interactions can be found <scene name='95/952699/Overview_hbonds_fixed/1'>here</scene> (highlighted in green). At a cellular pH, various amino acid residues found in the transmembrane region are charged as well, which strengthens the overall interaction. For example, <scene name='95/952699/N155_e138_hbonds_fixed/1'>a hydrogen bond</scene> between residues N155 and E138, along with numerous other hydrogen bonds, works to stabilize the α-β chain interactions. Further down the chains, <scene name='95/952699/T166_e148_hbonds_fixed/1'>interactions</scene> between residues T166 and E148 also have strong hydrogen bonding. Overall, these hydrogen bonds and ion interactions work to maintain the association of the α-β chains.
+Many transmembrane interactions can be found within a IgM B-cell receptor. The <scene name='95/952699/Transmembrane_region/1'>α and β subunits</scene> have numerous interactions that keep them associated with each other. An overview of all residue interactions can be found <scene name='95/952699/Overview_hbonds_fixed/2'>here</scene> (highlighted in green). At a cellular pH, various amino acid residues found in the transmembrane region are charged as well, which strengthens the overall interaction. For example, <scene name='95/952699/N155_e138_hbonds_fixed/2'>a hydrogen bond</scene> between residues N155 and E138, along with numerous other hydrogen bonds, works to stabilize the α-β chain interactions. Further down the chains, <scene name='95/952699/T166_e148_hbonds_fixed/2'>interactions</scene> between residues T166 and E148 also have strong hydrogen bonding. Overall, these hydrogen bonds and ion interactions work to maintain the association of the α-β chains.
 </StructureSection>