Abstract
Membrane proteins are challenging to study and restraints for structure determination are typically sparse or of low resolution because the membrane environment that surrounds them leads to a variety of experimental challenges. When membrane protein structures are determined by different techniques in different environments, a natural question is “which structure is most biologically relevant?” Towards answering this question, we compiled a dataset of membrane proteins with known structures determined by both solution NMR and X-ray crystallography. By investigating differences between the structures, we found that RMSDs between crystal and NMR structures are below 5 Å in the membrane region, NMR ensembles have a higher convergence in the membrane region, crystal structures typically have a straighter transmembrane region, have higher stereo-chemical correctness, and are more tightly packed. After quantifying these differences, we used high-resolution refinement of the NMR structures to mitigate them, which paves the way for identifying and improving the structural quality of membrane proteins.
Footnotes
Jeffrey J. Gray (jgray{at}jhu.edu) Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 208 Maryland Hall, 3400 North Charles Street, Baltimore, MD, 21218
Andrew R. D’Avino (drewdavino{at}gmail.com), Department of Chemical and Biomolecular Engineering Johns Hopkins University 3400 North Charles Street Baltimore, MD 21218
Yash Bhatnagar (yashdbhatnagar{at}gmail.com), Department of Chemical and Biomolecular Engineering Johns Hopkins University 3400 North Charles Street Baltimore, MD 21218
Abbreviations
- 30-Fos
- 2-undecylphosphocholine
- C8E4
- tetraethylene glycol monooctyl ether
- C8POE
- octyl-poly-oxyethylenoxide
- CHAPSO
- 3-([3-Cholamidopropyl]dimethylammonio)-2-hydroxy-1-propanesulfonate
- DDM
- n-dodecyl β-D-maltoside
- DePC
- decylphosphocholine
- DHPC
- dihexanoylphosphatidylcholine
- diC7PC
- 1,2-diheptanoyl-sn-glycero-phosphocholine
- DMPC
- 1,2-dimyristoyl-sn-glycero-phosphocholine
- DMSO
- dimethyl sulfoxide
- DPC
- n-dodecyl phosphatidylcholine
- LCP
- lipidic cubic phase
- LDAO
- lauryldimethylamine N-oxide
- OG
- octyl β-D-glucopyranoside
- SDS
- sodium dodecyl sulfate