The .beta.-trefoil protein human fibroblast growth factor-1 (FGF-1) is
made up of a six-stranded anti-parallel .beta.-barrel closed off on one
end by three .beta.-hairpins, thus exhibiting a three-fold axis of
structural symmetry. The N- and C-termini .beta.-strands hydrogen bond to
each other and are postulated from both NMR and X-ray structure data to
represent a structurally-weakened region of the .beta.-barrel. Val
mutations within the N- and C-termini .beta.-strands are shown to
stabilize the structure and to increase van der Waals contacts by filling
local cavities present within this region. Mutations that increase van
der Waals contacts between both the N- and C-termini .beta.-strands are
generally associated with significant reductions in the unfolding
kinetics, and also increase the cooperativity of unfolding. Surprisingly,
several mutant polypeptides herein disclosed greatly exceed the wild-type
polypeptide in ability to stimulate human fibroblasts to proliferate.