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Nat Methods. 2012 May 20;9(8):834-9. doi: 10.1038/nmeth.2033.

Facile backbone structure determination of human membrane proteins by NMR spectroscopy.

Author information

1
Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.

Abstract

Although nearly half of today's major pharmaceutical drugs target human integral membrane proteins (hIMPs), only 30 hIMP structures are currently available in the Protein Data Bank, largely owing to inefficiencies in protein production. Here we describe a strategy for the rapid structure determination of hIMPs, using solution NMR spectroscopy with systematically labeled proteins produced via cell-free expression. We report new backbone structures of six hIMPs, solved in only 18 months from 15 initial targets. Application of our protocols to an additional 135 hIMPs with molecular weight <30 kDa yielded 38 hIMPs suitable for structural characterization by solution NMR spectroscopy without additional optimization.

PMID:
22609626
PMCID:
PMC3723349
DOI:
10.1038/nmeth.2033
[Indexed for MEDLINE]
Free PMC Article

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