Premium
Crystal structure of a consensus‐designed ankyrin repeat protein: Implications for stability
Author(s) -
Binz H. Kaspar,
Kohl Andreas,
Plückthun Andreas,
Grütter Markus G.
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20930
Subject(s) - ankyrin repeat , ankyrin , protein crystallization , protein stability , computational biology , computer science , chemistry , biology , microbiology and biotechnology , genetics , organic chemistry , gene , crystallization
Consensus‐designed ankyrin repeat (AR) proteins are thermodynamically very stable. The structural analysis of the designed AR protein E3_5 revealed that this stability is due to a regular fold with highly conserved structural motifs and H‐bonding networks. However, the designed AR protein E3_19 exhibits a significantly lower stability than E3_5 (9.6 vs. 14.8 kcal/mol), despite 88% sequence identity. To investigate the structural correlations of this stability difference between E3_5 and E3_19, we determined the crystal structure of E3_19 at 1.9 Å resolution. E3_19 as well has a regular AR domain fold with the characteristic H‐bonding patterns. All structural features of the E3_5 and E3_19 molecules appear to be virtually identical (RMSD Cα ≈ 0.7 Å). However, clear differences are observed in the surface charge distribution of the two AR proteins. E3_19 features clusters of charged residues and more exposed hydrophobic residues than E3_5. The atomic coordinates of E3_19 have been deposited in the Protein Data Bank. PDB ID: 2BKG. Proteins 2006. © 2006 Wiley‐Liss, Inc.