Structure of the IgM B cell receptor of the mouse. Credit: Hao Wu/Harvard Medical School
Connection of Signaling Subunits with the Immunoglobulin
The B cell antigen receptor is comprised of an antibody connected to the cell membrane in addition to two smaller proteins referred to as Ig alpha and Ig beta. When the B cell receptor identifies a pathogen, these smaller subunits send signals to the cells interior.
” Exactly how these signaling subunits are gotten in touch with the immunoglobulin was formerly unknown,” says Prof. Dr. Michael Reth from the University of Freiburgs Faculty of Biology, who has actually been conducting research study on the receptor for over 30 years and originally found its signaling subunits. He is a member of the Cluster of Excellence CIBSS– Centre for Integrative Biological Signalling Studies and co-director of the Cluster of Excellence BIOSS.
” For a very long time, we did not have the technical possibilities to study the precise structure of membrane proteins. Now, cryo-electron microscopy has allowed us to create a high-resolution picture of the B cell receptor,” states Reth.
With cryo-electron microscopy, the sample to be studied is cooled really quickly to minus 183 ° C. This lowers the natural motion of the molecules and prevents the formation of tiny ice crystals that otherwise would ruin the protein structure. In this way, it is possible to attain resolutions that are lot of times greater than with other electron tiny techniques. In their present research study, the scientists achieved a resolution of 3.3 ångströms, which corresponds to the width of just a couple of atoms. To do so, they combined hundreds of thousands of pictures of the whole receptor with those of a truncated variation that lacked 2 flexible regions. They then used these information to determine the complete three-dimensional structure of the B cell receptor on the computer system.
An in proportion membrane-bound antibody binds just on one side
The striking aspect of the three-dimensional structure is that the balanced membrane-bound antibody just binds to Ig alpha and Ig beta on one side, therefore forming an unbalanced complex. This asymmetry looks like that of the T cell receptor, another crucial immune receptor whose structure was very first illuminated in 2019. “It is impressive that both types of antigen receptor form asymmetrical complexes,” explains Reth. “This leads us to conclude that the structure now illuminated becomes part of a bigger receptor complex which it interacts with still other molecules on the B cell surface area.”
Such bigger structures, which are held together through less effective forces, can not yet be studied with techniques like cryo-electron microscopy. Nevertheless, the recently released molecular structure provides more evidence in favor of such an interaction with other particles: It shows that the exterior of the B cell receptor includes saved amino acids. Amino acids are explained as saved if they barely alter in the course of advancement and are therefore similar in the antigen receptors of various organisms. “The existence of saved amino acids that are directed outside recommends that the IgM B cell receptor has further binding partners,” states Reth. “In other words, we just understand part of the machine so far– and now we desire to recognize the other building blocks and figure out how they affect the signaling result of the receptor.”
When it binds to an antigen, these other structure blocks might discuss how the receptor is normally kept quiescent and is triggered only. “That will be one of the next important jobs in the study of adaptive resistance,” sums up Reth. “A better understanding of B cell activation might likewise help us to more improve the advancement of vaccines or to understand the formation of lymphoma in which the B cell receptor is triggered in an unrestrained way.”
Recommendation: “Structural concepts of B cell antigen receptor assembly” by Ying Dong, Xiong Pi, Frauke Bartels-Burgahn, Deniz Saltukoglu, Zhuoyi Liang, Jianying Yang, Frederick W. Alt, Michael Reth and Hao Wu, 13 October 2022, Nature.DOI: 10.1038/ s41586-022-05412-7.
The research study was funded by the National Institutes of Health (NIH) and the German Research Foundation (DFG).
The researchers have exposed the specific molecular structure of an IgM-type B cell receptor.
Freiburg and Harvard University researchers have exposed the three-dimensional structure of the B cell antigen receptor, offering new insight into its composition.
B cells have antigen receptors on their surface that permit them to identify getting into pathogens such as bacteria and infections. When a B cell receptor binds to an antigen, that is, to a foreign structure, the B cell is activated which triggers the production of antibodies. Antibodies are important for human survival because they secure us from severe diseases from infections with pathogens such as COVID-19. Vaccines supply security by triggering antigen receptors, activating an immune action.
A global cooperation of scientists from the University of Freiburgs Cluster of Excellence CIBSS and Harvard Medical School in the United States has just recently revealed the precise molecular structure of an IgM-type B cell receptor. Their outcomes suggest that the B cells surface area receptor communicates with other receptors, therefore controlling signal transduction. The findings were just recently released in the distinguished journal Nature.
When a B cell receptor binds to an antigen, that is, to a foreign structure, the B cell is activated which activates the production of antibodies. A global collaboration of researchers from the University of Freiburgs Cluster of Excellence CIBSS and Harvard Medical School in the United States has just recently exposed the precise molecular structure of an IgM-type B cell receptor. Their results recommend that the B cells surface area receptor connects with other receptors, hence managing signal transduction. The freshly published molecular structure supplies further evidence in favor of such an interaction with other particles: It shows that the exterior of the B cell receptor includes saved amino acids. “A much better understanding of B cell activation might also assist us to additional improve the development of vaccines or to comprehend the development of lymphoma in which the B cell receptor is activated in an uncontrolled way.”
