1NQB

TRIVALENT ANTIBODY FRAGMENT

Summary for 1NQB

• Entry DOI: 10.2210/pdb1nqb/pdb
• Descriptor: SINGLE-CHAIN ANTIBODY FRAGMENT (2 entities in total)
• Functional Keywords: antibody fragment, multivalent antibody, diabody, domain swapping, immunoglobulin
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 56755.07

Authors

Williams, R.L.,Pei, X.Y. (deposition date: 1997-04-04, release date: 1997-08-20, Last modification date: 2024-10-16)

Primary citation

Pei, X.Y.,Holliger, P.,Murzin, A.G.,Williams, R.L.
The 2.0-A resolution crystal structure of a trimeric antibody fragment with noncognate VH-VL domain pairs shows a rearrangement of VH CDR3.
Proc.Natl.Acad.Sci.USA, 94:9637-9642, 1997

PubMed Abstract: The 2.0-A resolution x-ray crystal structure of a novel trimeric antibody fragment, a "triabody," has been determined. The trimer is made up of polypeptides constructed in a manner identical to that previously described for some "diabodies": a VL domain directly fused to the C terminus of a VH domain-i.e., without any linker sequence. The trimer has three Fv heads with the polypeptides arranged in a cyclic, head-to-tail fashion. For the particular structure reported here, the polypeptide was constructed with a VH domain from one antibody fused to the VL domain from an unrelated antibody giving rise to "combinatorial" Fvs upon formation of the trimer. The structure shows that the exchange of the VL domain from antibody B1-8, a Vlambda domain, with the VL domain from antibody NQ11, a Vkappa domain, leads to a dramatic conformational change in the VH CDR3 loop of antibody B1-8. The magnitude of this change is similar to the largest of the conformational changes observed in antibody fragments in response to antigen binding. Combinatorial pairing of VH and VL domains constitutes a major component of antibody diversity. Conformationally flexible antigen-binding sites capable of adapting to the specific CDR3 loop context created upon VH-VL pairing may be employed by the immune system to maximize the structural diversity of the immune response.

PubMed: 9275175
DOI: 10.1073/pnas.94.18.9637

Experimental method

X-RAY DIFFRACTION (2 Å)