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Determining membrane protein structures: Still a challenge!

INSERM, U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, Faculté de Médecine X. Bichat, Université Paris 7, BP 416, F-75018, Paris, France.
Trends in Biochemical Sciences (Impact Factor: 13.52). 07/2007; 32(6):259-70. DOI: 10.1016/j.tibs.2007.04.001
Source: PubMed

ABSTRACT Determination of structures and dynamics events of transmembrane proteins is important for the understanding of their function. Analysis of such events requires high-resolution 3D structures of the different conformations coupled with molecular dynamics analyses describing the conformational pathways. However, the solution of 3D structures of transmembrane proteins at atomic level remains a particular challenge for structural biochemists--the need for purified and functional transmembrane proteins causes a 'bottleneck'. There are various ways to obtain 3D structures: X-ray diffraction, electron microscopy, NMR and modelling; these methods are not used exclusively of each other, and the chosen combination depends on several criteria. Progress in this field will improve knowledge of ligand-induced activation and inhibition of membrane proteins in addition to aiding the design of membrane-protein-targeted drugs.

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Available from: Jean-Jacques Lacapere, Jul 28, 2015
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    • "Structural studies of membrane protein are intricate and several approaches are possible [12]. Among them, electron microscopy can be used to study membrane protein organization within the artificial membranes either by two-dimensional crystallization in solution or by reorganization of adsorbed proteins under a lipid monolayer at the air/water interface [13] [14] [15]. "
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    • "This is the first report, to our knowledge, of the successful expression of recombinant hENT1 (N-HAT-3ÂFLAG- hENT1) in a bacterial host. This is a significant step towards three-dimensional analysis of hENT1, a clinically important drug transporter, because it represents an important step towards overcoming the problem of low yields of mammalian ENTs and producing sufficient concentrations of protein (up to 10 mg/mL) for future structural studies (Lacapère et al. 2007). This approach can be scaled up and uses a lac promoter to drive expression plus tandem affinity purification to isolate N-HAT-3ÂFLAG-hENT1. "
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    • "This may be obtained with the help of a structural alphabet (Offmann et al. 2007; Joseph et al. 2010) as it has been used for defining DARC structural model (de Brevern et al. 2005; de Brevern 2009; de Brevern et al. 2009). The results herein described are quite important for molecular modelling of transmembrane proteins (de Graaf and Rognan 2009; Mornon et al. 2009), which are major medical drug targets, (Jacoby et al. 2006; Lacapere et al. 2007; Landry and Gies 2008; Arinaminpathy et al. 2009) and to improve protein topology prediction approaches (Harrington and Ben-Tal 2009; Klammer et al. 2009; Nugent and Jones 2009). "
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