1RJC

Crystal structure of the camelid single domain antibody cAb-Lys2 in complex with hen egg white lysozyme

Summary for 1RJC

• Entry DOI: 10.2210/pdb1rjc/pdb
• Related: 1RI8
• Descriptor: camelid heavy chain antibody, Lysozyme C, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: beta sandwich, immunoglobulin fold, protein-protein hetero complex, alpha-beta orthogonal bundle, immune system-hydrolase complex, immune system/hydrolase
• Biological source: Camelus dromedarius (Arabian camel); More
• Cellular location: Secreted: P00698
• Total number of polymer chains: 2
• Total formula weight: 29420.52

Authors

De Genst, E.,Silence, K.,Ghahroudi, M.A.,Decanniere, K.,Loris, R.,Kinne, J.,Wyns, L.,Muyldermans, S. (deposition date: 2003-11-19, release date: 2005-02-01, Last modification date: 2024-11-20)

Primary citation

De Genst, E.,Silence, K.,Ghahroudi, M.A.,Decanniere, K.,Loris, R.,Kinne, J.,Wyns, L.,Muyldermans, S.
Strong in vivo maturation compensates for structurally restricted H3 loops in antibody repertoires.
J.Biol.Chem., 280:14114-14121, 2005

PubMed Abstract: A central paradigm in immunology states that successful generation of high affinity antibodies necessitates an immense primary repertoire of antigen-combining sites. Much of the diversity of this repertoire is provided by varying one antigen binding loop, created by inserting randomly a D (diversity) gene out of a small pool between the V and J genes. It is therefore assumed that any particular D-encoded region surrounded by different V and J regions adopts a different conformation. We have solved the structure of two lysozyme-specific variable domains of heavy-chain antibodies isolated from two strictly unrelated dromedaries. These antibodies recombined identical D gene sequences to different V and J precursors with significant variance in their V(D)J junctions. Despite these large differences, the D-encoded loop segments adopt remarkably identical architectures, thus directing the antibodies toward identical epitopes. Furthermore, a striking convergent maturation process occurred in the V region, adapting both binders for their sub-nanomolar affinity association with lysozyme. Hence, on a structural level, humoral immunity may rely more on well developed maturation and selection systems than on the acquisition of large primary repertoires.

PubMed: 15659390
DOI: 10.1074/jbc.M413011200

Experimental method

X-RAY DIFFRACTION (1.4 Å)