One sequence, four folds: transitions between an ensemble of metastable folds for the N-terminal domain of CD2.
Recombinant forms of the N-terminal domain of the cell adhesion receptor CD2 adopt a variety of olds by exchange of beta-sheets between adjacent polypeptide chains. Although these interdigitated forms are normally metastable, we have used site-directed mutagenesis to alter the kinetics of formation and relative stabilities of these states, leading to spontaneous formation of monomeric, dimeric, trimeric and tetrameric intertwined folded states. A characteristic feature of these fold-disorder-alternative fold transitions is the independence of each domain folding event, as deduced from kinetic analysis of folding data. Structures for fully interdigitated trimeric and tetrameric forms have been modelled, consistent with both the crystallographic and kinetic data. Although the biological role of these alternative folded states remains unclear, these structures form a remarkable demonstration of the fluidity of structure generated from a single polypeptide chain.
Sessions
R B
RB
Department of Biochemistry, University of Bristol, U.K.
Hayes
M V
MV
Murray
A J
AJ
Clarke
A R
AR
Brady
R L
RL
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018801:CD2 Antigens / Q000737:chemistry*; D003196:Computer Graphics; D019281:Dimerization; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011381:Programming Languages; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017384:Sequence Deletion
D018801:CD2 Antigens; D011994:Recombinant Proteins