[[File:ScFv-rotation.gif|thumb|Rotating scFv fragment with highlighted complementary determining regions (CDRs)]]
[[File:Single chain variable fragment.svg|thumb|The two possible structures of a single-chain variable fragment, with the antigen binding sites including the [[N-terminus|N-termini]] on the left and the [[C-terminus|C-termini]] on the right. The linker peptides are shown as arrows.]]
A '''single-chain variable fragment''' ('''scFvscvF''') is not actually a fragment of an antibody, but instead is a [[fusion protein]] of the variable regions of the [[Immunoglobulin heavy chain|heavy]] (V<sub>H</sub>) and [[Immunoglobulin light chain|light chains]] (V<sub>L</sub>) of [[immunoglobulins]], connected with a short linker [[peptide]] of ten to about 25 [[amino acid]]s.<ref>{{cite journal | last1 = Huston | first1 = J. S. | last2 = Levinson | first2 = D. | last3 = Mudgett-Hunter | first3 = M. | last4 = Tai | first4 = M. S. | last5 = Novotný | first5 = J. | last6 = Margolies | first6 = M. N. | last7 = Crea | first7 = R. | year = 1988 | title = Protein engineering of antibody binding sites: recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli | url = | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 16| pages = 5879–5883 | doi=10.1073/pnas.85.16.5879| pmid = 3045807 | pmc = 281868 }}</ref> The linker is usually rich in [[glycine]] for flexibility, as well as [[serine]] or [[threonine]] for solubility, and can either connect the [[N-terminus]] of the V<sub>H</sub> with the [[C-terminus]] of the V<sub>L</sub>, or ''vice versa''.<ref name="Schirrmann">{{cite web|url=http://edoc.hu-berlin.de/dissertationen/schirrmann-thomas-2005-03-18/HTML/|language=German|last=Schirrmann|first=Thomas|title=Tumorspezifisches Targeting der humanen Natürlichen Killerzellinie YT durch Gentransfer chimärer Immunglobulin-T-Zellrezeptoren|date=8 November 2004|___location=Berlin}}</ref>
This protein retains the specificity of the original immunoglobulin, despite removal of the constant regions and the introduction of the linker.<ref name="Peterson" /> The image to the right shows how this modification usually leaves the specificity unaltered.
