Membrane Proteins

The high peak brightness of LCLS enables the structural determination of membrane proteins, which often form only microcrystals.

Understanding membrane proteins

Membrane proteins are a broad class of proteins that often work as molecular machines. These “machines” perform diverse functions, such as ion transport or signal transduction, by undergoing structural rearrangements. Crystallography is used to provide a better understanding of how these proteins function.

Extremely bright light sources, such as the Linac Coherent Light Source (LCLS), make it possible to capture time-resolved molecular snapshots of these proteins at different time points in their functional cycle. The structural changes can then be related to their biological function.

Membrane proteins carry out diverse roles in biology, such as transport, signal transduction, catalysis, or anchoring the cell.

Membrane proteins carry out diverse roles in biology, such as transport, signal transduction, catalysis, or anchoring the cell. Figure provided by Scitable, Nature Education.

Current issues to overcome

Membrane proteins are often difficult to crystallize. Even if the crystallization conditions of the protein are known, it can be almost impossible to grow large, well-ordered crystals. The resulting membrane protein microcrystals can sometimes be difficult to study at the synchrotron, because of the limited brightness of the light source.

Moreover, microcrystals of membrane proteins tend to be more prone to X-ray radiation damage than large crystals grown from soluble proteins. Typically, when using synchrotrons, cryogenic temperatures are used to mitigate radiation damage. However, imaging the samples at non-native temperatures can induce non-native conformations in amino acid side chains.

How LCLS can help

Fortunately, X-ray free-election lasers (XFELs) like the Linac Coherent Light Source (LCLS) have largely solved these problems by allowing the study of proteins at near-native conditions (room temperature), and the ability to use small crystals (<10 µm). This opens new opportunities for studying the dynamics, kinetics, and function of membrane proteins. G-Protein Coupled Receptors (GPCRs) have been the flagship for showing how XFELs can help research into membrane proteins.

Graphic of prominent GPCR structures solved at LCLS between 2013 (the first GPCR structure solved at the XFEL) and 2019. Image supplied by Vadin Cherezov.


Latest publications

The following publications highlight how membrane proteins have been studied at LCLS:


Ion Pumps


Lipopolysaccharide biogenesis in Gram-negative bacteria