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An unexpected outcome of surface engineering an integral membrane protein: improved crystallization of cytochrome ba{sub 3} from Thermus thermophilus

Journal Article · · Acta Crystallographica. Section F
Mutation of symmetry-related (in space group P4{sub 3}2{sub 1}2) glutamate and lysine residues on the water-exposed surface of an integral membrane protein, cytochrome ba{sub 3}, from T. thermophilus leads to robust crystallization of the protein in space group P4{sub 1}2{sub 1}2; crystals of these mutant proteins show X-ray diffraction to molecular resolution. Past work has shown that it is feasible to mutate surface residues of soluble proteins and to a lesser extent membrane proteins in order to improve their crystallization behavior. Described here is a successful application of this approach to the integral membrane protein Thermus thermophilus cytochrome ba{sub 3} oxidase. Two mutant forms of this enzyme (I-K258R and I-K258R/II-E4Q) were created in which symmetrical crystal contacts within crystals of wild-type enzyme were modified. These mutant proteins had greatly shortened crystallization times, decreasing from ∼30 d for the wild type to 1–3 d for the mutants, and crystallization was highly reproducible. Native-like proteins crystallize in space group P4{sub 3}2{sub 1}2, whereas the mutant proteins crystallize in space group P4{sub 1}2{sub 1}2 with a different packing arrangement. Crystals of the P4{sub 3}2{sub 1}2 form occasionally diffracted to 2.4–2.3 Å resolution following controlled dehydration, while those of the P4{sub 1}2{sub 1}2 form routinely diffracted to between 3.0 and 2.6 Å for crystals that had been cryoprotected but not dehydrated.
OSTI ID:
22360436
Journal Information:
Acta Crystallographica. Section F, Journal Name: Acta Crystallographica. Section F Journal Issue: Pt 12 Vol. 63; ISSN ACSFCL; ISSN 1744-3091
Country of Publication:
United Kingdom
Language:
English