[대학원 생명과학과 세미나 안내]
연사 : 이지오 교수(KAIST 화학과)
연제 : Crystallizing uncrystallizable proteins
일시 : 2017년 6월 2일 (금) 오후 4시
장소 : 하나과학관 A동 109호
초청교수 : 송현규 교수
Many proteins and protein complexes, including transmembrane or large protein complexes, are notoriously difficult to crystallize. Antibody Fab domains have been proved useful as crystallization chaperones that can improve crystallization behavior of such challenging proteins by providing a new crystallization surface or hiding regions harmful for crystallization. Crystallization chaperones are usually connected to their target proteins by flexible linkers. This does not always improve the crystallization behavior of the target-chaperone fusion proteins because the great structural flexibility of the linker usually diminishes the crystallization behavior of the fusion proteins. We proposed that diabodies, a form of engineered bispecific antibodies, have rigid structures and can serve as ideal linkers connecting targets and crystallization chaperones.
Diabodies, particularly those stabilized by an interface disulfide bridge, can be more useful for protein crystallization than simple Fab domains for the following reasons. First, they have all the advantage possessed by Fab domains; they can hide harmful surface areas and provide ones effective for crystallization. Second, diabodies, particularly those stabilized by a disulfide bridge in the Fv interface, should be able to link target proteins and crystallization chaperones in a rigid and crystallizable fashion. By screening many crystallization “chaperones” and the diabodies connecting them to target proteins, one might be able to find the most suitable target-diabody-chaperone complex for generating crystals suitable for high resolution structure determination. One would not have to produce additional antibody clones against the target protein because one would only need to change one of the Fv domains that bind to the chaperone.