Structural insight into pre-B cell receptor function.
The pre-B cell receptor (pre-BCR) serves as a checkpoint in B cell development. In the 2.7 angstrom structure of a human pre-BCR Fab-like fragment, consisting of an antibody heavy chain (HC) paired with the surrogate light chain, the "unique regions" of VpreB and lambda5 replace the complementarity-determining region 3 (CDR3) loop of an antibody light chain and appear to "probe" the HC CDR3, potentially influencing the selection of the antibody repertoire. Biochemical analysis indicates that the pre-BCR is impaired in its ability to recognize antigen, which, together with electron microscopic visualization of a pre-BCR dimer, suggests ligand-independent oligomerization as the likely signaling mechanism.
Bankovich
Alexander J
AJ
Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Raunser
Stefan
S
Juo
Z Sean
ZS
Walz
Thomas
T
Davis
Mark M
MM
Garcia
K Christopher
KC
D000818:Animals; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000502:physiology; D018360:Crystallography, X-Ray; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000502:physiology; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000502:physiology; D054444:Immunoglobulin Light Chains, Surrogate; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008958:Models, Molecular; D054420:Pre-B Cell Receptors; D011487:Protein Conformation; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins