Incorporation of Long CDR3s into V Domains: Implications for the Structural Evolution of the Antibody-Combining SiteRamsland P.A. · Kaushik A. · Marchalonis J.J. · Edmundson A.B.
aCrystallography Program, Oklahoma Medical Research Foundation, OklahomaCity, Okla., USA; bDepartment of Pathobiology, University of Guelph,Ont., Canada; cDepartment of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson,Ariz., USA; dStructural Biology Laboratory, The Austin Research Institute, Heidelberg, Vic., Australia
Available data suggest that ‘primitive’ antibody-combining sites often include longer than average HCDR3s. Long HCDR3 sequences have been reported in diverse vertebrates, including humans, cattle, camels and sharks. These long HCDR3 segments contain unusual sequence features such as stretches of Gly or Pro residues and multiple Cys residues. We examined how longer than average HCDR3s were accommodated in the V domains of human, murine and camel antibodies with known three-dimensional structures. The main conclusions were that (1) HCDR3s longer than 12 residues should protrude outward from the V domains; (2) descending HCDR3 polypeptides may utilize VL (including LCDR3) constituents as a platform, supporting the protruding segments; (3) intra- and inter-HCDR disulfides are frequently formed to rigidify the structure of HCDR3 or the combining site, and (4) V and C domains were possibly more similar in primordial antibodies than they are in their present day counterparts.
Allen B. Edmundson, PhD
Crystallography Program, Oklahoma Medical Research Foundation
825 NE 13th Street, Oklahoma City, OK 73104 (USA)
Tel. +1 405 271 1673, Fax +1 405 271 7953
Received: Received: June 21, 2001
Number of Print Pages : 23
Number of Figures : 9, Number of Tables : 2, Number of References : 100
Experimental and Clinical Immunogenetics
Vol. 18, No. 4, Year 2001 (Cover Date: Released Feburary 2002)
Journal Editor: K. Bauer, Heidelberg
ISSN: 0254–9670 (print), 1421–9948 (Online)
For additional information: http://www.karger.com/journals/eci