cover illustration Top7, a de novo designed protein with high thermal and chemical stability, was modified to bind human CD4 by elongating an existing loop with a sequence (CB1) derived from a complementary determining region of an anti-CD4 antibody. The resulting protein (Top7_CB1), like Top7, is extremely stable and can withstand chemical and thermal conditions that denature most proteins. These results demonstrate Top7's potential as a scaffold for constructing robust, non-antibody based affinity reagents. The cover shows the structure of Top7_CB1 with the 10 best scored modeled conformations of the inserted CD4-binding region (CB1) in yellow. For further details please see Boschek et al. pp. 325-332.