Sandbox Reserved 1787: Difference between revisions
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=='''Introduction'''== | =='''Introduction'''== | ||
The [https://en.wikipedia.org/wiki/Adaptive_immune_system adaptive immune response] possessed by [https://en.wikipedia.org/wiki/Vertebrate vertebrate] animals owes much of its function to [https://en.wikipedia.org/wiki/B_cell B cells]. These specialized immune cells produce [https://en.wikipedia.org/wiki/Antibody antibodies] and | The [https://en.wikipedia.org/wiki/Adaptive_immune_system adaptive immune response] possessed by [https://en.wikipedia.org/wiki/Vertebrate vertebrate] animals owes much of its function to [https://en.wikipedia.org/wiki/B_cell B cells]. These specialized immune cells produce [https://en.wikipedia.org/wiki/Antibody antibodies] and immunoglobulins (Ig), the membrane bound equivalent to antibodies. B cells can produce a variety of Ig compounds including [https://en.wikipedia.org/wiki/Immunoglobulin_G IgG], [https://en.wikipedia.org/wiki/Immunoglobulin_A IgA], [https://en.wikipedia.org/wiki/Immunoglobulin_E IgE], [https://en.wikipedia.org/wiki/Immunoglobulin_D IgD], and [https://en.wikipedia.org/wiki/Immunoglobulin_M IgM]. These antibodies and Ig compounds bind to specific compounds called [https://en.wikipedia.org/wiki/Antigen antigens]. When an IgM combines with a [https://en.wikipedia.org/wiki/B-cell_receptor B cell receptor] (BCR), it can then send a signal in the form of a conformational change through the B cell membrane to stimulate the production of more antibodies that recognize that antigen. <ref name="Sathe">Sathe A, Cusick JK. Biochemistry, Immunoglobulin M. 2022 Dec 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32310455. https://pubmed.ncbi.nlm.nih.gov/32310455/</ref> | ||
The structure of the IgM BCR complex was determined by two research groups using [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy Cryo EM]. They also determined the structure of IgG. <ref name="Su">PMID:35981043</ref>, <ref name="Ma">PMID:35981028</ref> | The structure of the IgM BCR complex was determined by two research groups using [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy Cryo EM]. They also determined the structure of IgG. <ref name="Su">PMID:35981043</ref>, <ref name="Ma">PMID:35981028</ref> | ||
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The constant region of IgM is made up of the two <scene name='95/952714/Heavy_chain/1'>heavy chains</scene>. These heavy chains form a bridge connecting the FAB region or variable region to the transmembrane region (Figure 1). They also act as a wire that the variable region can send a signal through to the transmembrane region as a mechanical change. | The constant region of IgM is made up of the two <scene name='95/952714/Heavy_chain/1'>heavy chains</scene>. These heavy chains form a bridge connecting the FAB region or variable region to the transmembrane region (Figure 1). They also act as a wire that the variable region can send a signal through to the transmembrane region as a mechanical change. | ||
<scene name='95/ | <scene name='95/952715/Extracellular_transmembrane_v2/10'>Extracellular transmembrane region interactions</scene> help hold the heavy chains and <b><span class="text-brown">Igα</span></b>/<b><span class="text-orange">Igβ</span></b> chains together in the extracellular portion of the transmembrane region. Because a conformational change occurs throughout the entirety of the IgM-BCR complex, the Fc region must be able to tolerate the contortion of the structure as the antigen binds. In constant region two, which is located at the start of the Fc region, '''{{Font color|violet|heavy chain A}}''' and <b><span class="text-blue">heavy chain B</span></b> make a <scene name='95/952713/Disulfides/5'>disulfide bridge</scene> to stabilize the IgM-BCR and drive downstream signaling. | ||
To maximize the Fc region’s signal transduction efficiency and Van der Waals contacts, constant region two of '''{{Font color|violet|heavy chain A}}''' makes an asymmetrical association with constant region three of <b><span class="text-blue">heavy chain B</span></b> to create a <scene name='95/952713/Trans_heavy/7'>heavy chain interface</scene>. More specifically, Arg243 and Arg251 residues from '''{{Font color|violet|heavy chain A}}''' donate three hydrogen bonds to Leu433, Thr431, and Asp376 residues on <b><span class="text-blue">heavy chain B</span></b>. Furthermore, Leu313 of'''{{Font color|violet|heavy chain A}}''' accepts a hydrogen bond from Thr429 on <b><span class="text-blue">heavy chain B</span></b>. <ref name="Ma">PMID:35981028</ref> | |||
To maximize the Fc region’s signal transduction efficiency and Van der Waals contacts, constant region two of '''{{Font color|violet|heavy chain A}}''' makes an asymmetrical association with constant region three of <b><span class="text-blue">heavy chain B</span></b> to create a <scene name='95/952713/Trans_heavy/7'>heavy chain interface</scene>. More specifically, Arg243 and Arg251 residues from '''{{Font color|violet|heavy chain A}}''' donate three hydrogen bonds to Leu433, Thr431, and Asp376 residues on <b><span class="text-blue">heavy chain B</span></b>. Furthermore, Leu313 of heavy chain A accepts a hydrogen bond from Thr429 on heavy chain B. <ref name="Ma">PMID:35981028</ref> | |||
===Fab Region=== | ===Fab Region=== | ||
