The crystal structure of Aspergillus fumigatus cyclophilin reveals 3D domain swapping of a central element.
The crystal structure of Aspergillus fumigatus cyclophilin (Asp f 11) was solved by the multiwavelength anomalous dispersion method and was refined to a resolution of 1.85 A with R and R(free) values of 18.9% and 21.4%, respectively. Many cyclophilin structures have been solved to date, all showing the same monomeric conformation. In contrast, the structure of A. fumigatus cyclophilin reveals dimerization by 3D domain swapping and represents one of the first proteins with a swapped central domain. The domain-swapped element consists of two beta strands and a subsequent loop carrying a conserved tryptophan. The tryptophan binds into the active site, inactivating cis-trans isomerization. This might be a means of biological regulation. The two hinge loops leave the protein prone to misfolding. In this context, alternative forms of 3D domain swapping that can lead to N- or C-terminally swapped dimers, oligomers, and aggregates are discussed.
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
Andreas
A
Limacher
Daniel P
DP
Kloer
Sabine
S
Flückiger
Gerd
G
Folkers
Reto
R
Crameri
Leonardo
L
Scapozza
D000595:Amino Acid Sequence; D001232:Aspergillus fumigatus / Q000201:enzymology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D021983:Cyclophilins / Q000737:chemistry*; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D005656:Fungal Proteins; D021983:Cyclophilins