3PHO

Crystal structure of S64-4 in complex with PSBP

Summary for 3PHO

• Entry DOI: 10.2210/pdb3pho/pdb
• Related: 3PHQ
• Descriptor: S64-4 Fab (IgG1) light chain, S64-4 Fab (IgG1) heavy chain, 3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid-(2-8)-3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid-(2-4)-3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid-(2-6)-2-amino-2-deoxy-4-O-phosphono-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: antibody, fab, igg, carbohydrate, carbohydrate-binding protein
• Biological source: Mus musculus; More
• Total number of polymer chains: 2
• Total formula weight: 48599.79

Authors

Evans, D.W.,Evans, S.V. (deposition date: 2010-11-04, release date: 2011-05-18, Last modification date: 2024-10-16)

Primary citation

Evans, D.W.,Muller-Loennies, S.,Brooks, C.L.,Brade, L.,Kosma, P.,Brade, H.,Evans, S.V.
Structural insights into parallel strategies for germline antibody recognition of lipopolysaccharide from Chlamydia.
Glycobiology, 21:1049-1059, 2011

PubMed Abstract: The structure of the antigen-binding fragment from the monoclonal antibody S64-4 in complex with a pentasaccharide bisphosphate fragment from chlamydial lipopolysaccharide has been determined by x-ray diffraction to 2.6 Å resolution. Like the well-characterized antibody S25-2, S64-4 displays a pocket formed by the residues of germline sequence corresponding to the heavy and light chain V gene segments that binds the terminal Kdo residue of the antigen; however, although S64-4 shares the same heavy chain V gene segment as S25-2, it has a different light chain V gene segment. The new light chain V gene segment codes for a combining site that displays greater affinity, different specificity, and allows a novel antigen conformation that brings a greater number of antigen residues into the combining site than possible in S25-2. Further, while antibodies in the S25-2 family use complementarity determining region (CDR) H3 to discriminate among antigens, S64-4 achieves its specificity via the new light chain V gene segment and resulting change in antigen conformation. These structures reveal an intriguing parallel strategy where two different combinations of germline-coded V gene segments can act as starting points for the generation of germline antibodies against chlamydial antigens and show how anti-carbohydrate antibodies can exploit the conformational flexibility of this class of antigens to achieve high affinity and specificity independently of CDR H3.

PubMed: 21543444
DOI: 10.1093/glycob/cwr041

Experimental method

X-RAY DIFFRACTION (2.6 Å)