5DRW

Crystal structure of the BCR Fab fragment from subset #4 case CLL183

Summary for 5DRW

• Entry DOI: 10.2210/pdb5drw/pdb
• Descriptor: CLL183 BCR antibody heavy chain, CLL183 BCR antibody light chain (3 entities in total)
• Functional Keywords: immunoglobulin fold, b-cell receptor, chronic lymphocytic leukemia, immune system, receptor-ligand complex
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 48305.82

Authors

Minici, C.,Degano, M. (deposition date: 2015-09-16, release date: 2016-09-28, Last modification date: 2024-10-16)

Primary citation

Minici, C.,Gounari, M.,Ubelhart, R.,Scarfo, L.,Duhren-von Minden, M.,Schneider, D.,Tasdogan, A.,Alkhatib, A.,Agathangelidis, A.,Ntoufa, S.,Chiorazzi, N.,Jumaa, H.,Stamatopoulos, K.,Ghia, P.,Degano, M.
Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia.
Nat Commun, 8:15746-15746, 2017

PubMed Abstract: Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR-BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones. The diversity of homotypic BcR contacts leading to cell-autonomous signalling reconciles the existence of a shared pathogenic mechanism with the biological and clinical heterogeneity of CLL and offers opportunities for innovative treatment strategies.

PubMed: 28598442
DOI: 10.1038/ncomms15746

Experimental method

X-RAY DIFFRACTION (2.27 Å)