Membrane scaffold proteins

Details Membrane scaffold proteins Membrane scaffold proteins

C - Chemistry, Metallurgy

12

N

C12N 15/12 (2006.01) C07K 14/435 (2006.01) C07K 14/47 (2006.01) C07K 14/705 (2006.01) C07K 19/00 (2006.01) C12N 15/63 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2429473

Membrane proteins are difficult to express in recombinant form, purify, and characterize, at least in part due to their hydrophobic or partially hydrophobic properties. Membrane scaffold proteins (MSP) assemble with target membrane or other hydrophobic or partially hydrophobic proteins or membrane fragments to form soluble nanoscale particles which preserve their native structure and function; they are improved over liposomes and detergent micelles. In the presence of phospholipid, MSPs form nanoscopic phospholipid bilayer disks, with the MSP stabilizing the particle at the perimeter of the bilayer domain. The particle bilayer structure allows manipulation of incorporated proteins in solution or on solid supports, including for use with such surface-sensitive techniques as scanning probe microscopy or surface plasmon resonance. The nanoscale particles facilitate pharmaceutical and biological research, structure/function correlation, structure determination, bioseparation, and drug discovery.

Les protéines membranaires sont difficiles à exprimer sous forme recombinante, à purifier et à caractériser, au moins en partie à cause de leurs propriétés hydrophobes ou partiellement hydrophobes. Des protéines d'échaufaudage membranaires (MSP) s'assemblent à des membranes cibles ou d'autres protéines hydrophobes ou partiellement hydrophobes ou des fragments membranaires pour former des particules solubles à l'échelle nanométrique qui conservent leur structure et leur fonction d'origine. Elles sont améliorées par rapport à des liposomes et des micelles détergentes. En présence de phospholipides, les MSP forment des disques bicouches nanoscopiques phospholipidiques, la MSP stabilisant la particule sur le périmètre du domaine bicouche. La structure bicouche particulaire permet une manipulation de protéines incorporées en solution ou sur des supports solides, dont l'utilisation avec des techniques sensibles à la surface, telles que la microscopie-sonde à balayage ou la détection par résonance plasmonique de surface. Les particules à l'échelle nanométrique facilitent la recherche pharmaceutique et biologique, la corrélation structure/fonction, la détermination de structure, la bioséparation et la découverte de médicaments.

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