Polyamines Mediate Folding of Primordial Hyperacidic Helical Proteins

The mitochondrial outer membrane contains proteinaceous machineries for the import and assembly of proteins, including TOM (translocase of the outer membrane) and SAM (sorting and assembly machinery). It has been shown that the dimeric phospholipid cardiolipin is required for the stability of TOM and SAM complexes and thus for the efficient import and assembly of β-barrel proteins and some α-helical proteins of the outer membrane. Here, we report that mitochondria deficient in phosphatidylethanolamine (PE), the second non-bilayer-forming phospholipid, are impaired in the biogenesis of β-barrel proteins, but not of α-helical outer membrane proteins. The stability of TOM and SAM complexes is not disturbed by the lack of PE. By dissecting the import steps of β-barrel proteins, we show that an early import stage involving translocation through the TOM complex is affected. In PE-depleted mitochondria, the TOM complex binds precursor proteins with reduced efficiency. We conclude that PE is required for the proper function of the TOM complex.

Download Full-text

Universal nature of collapsibility in the context of protein folding and evolution

10.1101/461046 ◽

2018 ◽

Cited By ~ 1

Author(s):

D. Thirumalai ◽

Himadri S. Samanta ◽

Hiranmay Maity ◽

Govardhan Reddy

Keyword(s):

Single Molecule ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Saxs Data ◽

X Ray ◽

Model Free ◽

X Ray Scattering ◽

Theoretical Predictions ◽

Helical Proteins ◽

Universal Nature

AbstractTheory and simulations predicted sometime ago that the sizes of unfolded states of globular proteins should decrease continuously as the denaturant concentration is shifted from a high to a low value. However, small angle X-ray scattering (SAXS) data were used to assert the opposite, while interpretation of single molecule Forster resonance energy transfer experiments (FRET) supported the theoretical predictions. The disagreement between the two experiments is the SAXS-FRET controversy. By harnessing recent advances in SAXS and FRET experiments and setting these findings in the context of a general theory and simulations, we establish that compaction of unfolded states is universal. The theory also predicts that proteins rich in β-sheets are more collapsible than α-helical proteins. Because the extent of compaction is small, experiments have to be accurate and their interpretations should be as model free as possible. Theory also suggests that collapsibility itself could be a physical restriction on the evolution of foldable sequences, and provides a physical basis for the origin of multi-domain proteins.

Download Full-text