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Originally published in Science Express on 19 August 2004
Science 17 September 2004:
Vol. 305. no. 5691, pp. 1770 - 1773
DOI: 10.1126/science.1101148
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Reports

Crystal Structure of a Shark Single-Domain Antibody V Region in Complex with Lysozyme

Robyn L. Stanfield,1* Helen Dooley,3* Martin F. Flajnik,3 Ian A. Wilson1,2{dagger}

Cartilaginous fish are the phylogenetically oldest living organisms known to possess components of the vertebrate adaptive immune system. Key to their immune response are heavy-chain, homodimeric immunoglobulins called new antigen receptors (IgNARs), in which the variable (V) domains recognize antigens with only a single immunoglobulin domain, akin to camelid heavy-chain V domains. The 1.45 angstrom resolution crystal structure of the type I IgNAR V domain in complex with hen egg-white lysozyme (HEL) reveals a minimal antigen-binding domain that contains only two of the three conventional complementarity-determining regions but still binds HEL with nanomolar affinity by means of a binding interface comparable in size to conventional antibodies.

1 Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
3 Department of Microbiology and Immunology, University of Maryland at Baltimore, Baltimore, MD 21201–1559, USA, and the National Aquarium in Baltimore, 501 E. Pratt Street, Baltimore, MD 21202, USA.



Note added in proof: While this paper was in production, a paper reporting the structures of the two unliganded type 2 IgNAR variable domains was published (42).

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: wilson{at}scripps.edu

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