Modeling of the structural features of integral-membrane proteins using reverse-environment prediction of integral membrane protein structure (REPIMPS)

Dastmalchi, S Morris, MB Church, WB

S. Dastmalchi et al., Modeling of the structural features of integral-membrane proteins using reverse-environment prediction of integral membrane protein structure (REPIMPS), PROTEIN SCI, 10(8), 2001, pp. 1529-1538

71

INGLESE

Article

Biochemistry & Biophysics

PROTEIN SCIENCE

0961-8368 → ACNP

10

8

2001

1529 - 1538

ISI

0961-8368(200108)10:8<1529:MOTSFO>2.0.ZU;2-1

The Profiles-3D application, an inverse-folding methodology appropriate for water-soluble proteins, has been modified to allow the determination of st ructural properties of integral-membrane proteins (IMPs) and for testing th e validity of served and model structures of IMPs. The modification, known as reverse-environment prediction of integral membrane protein structure (R EPIMPS), takes into account the fact that exposed areas of side chains for many residues in IMPs are in contact with lipid and not the aqueous phase. This (1) allows lipid-exposed residues to be classified into the correct ph ysicochemical environment class, (2) significantly improves compatibility s cores for IMPs whose structures have been solved, and (3) reduces the possi bility of rejecting a three-dimensional structure for an IMP because the pr esence of lipid was not included. Validation tests of REPIMPS showed that i t (1) can locate the transmembrane domain of IMPs with single transmembrane helices more frequently than a range of other methodologies, (2) can rotat ionally orient transmembrane helices with respect to the lipid environment and surrounding helices in IMPs with multiple transmembrane helices, and (3 ) has the potential to accurately locate transmembrane domains in IMPs with multiple transmembrane helices. We conclude that correcting for the presen ce of the lipid environment surrounding the transmeembrane segments of IMPs is an essential step for reasonable modeling and verification of the three -dimensional structures of these proteins.