Engineering an intertwined form of CD2 for stability and assembly.
The amino-terminal domain of CD2 has the remarkable ability to fold in two ways: either as a monomer or as an intertwined, metastable dimer. Here we show that it is possible to differentially stabilize either fold by engineering the CD2 sequence, mimicking random mutagenesis events that could occur during molecular evolution. Crystal structures of a hinge-deletion mutant, which is stable as an intertwined dimer, reveal domain rotations that enable the protein to further assemble to a tetramer. These results demonstrate that a variety of folds can be adopted by a single polypeptide sequence, and provide guidance for the design of proteins capable of further assembly.
Murray
A J
AJ
Department of Biochemistry and Centre for Molecular Recognition, University of Bristol, University Walk, UK.
Head
J G
JG
Barker
J J
JJ
Brady
R L
RL
D000818:Animals; D018801:CD2 Antigens / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D004355:Drug Stability; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011487:Protein Conformation; D015202:Protein Engineering; D017510:Protein Folding; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion; D055672:Static Electricity
D018801:CD2 Antigens; D011994:Recombinant Proteins