Molecular mechanisms of steric pressure generation and membrane remodeling by disordered proteins

Justin R. Houser, Hyun Woo Cho, Carl C. Hayden, Noel X. Yang, Liping Wang, Eileen M. Lafer, Dave Thirumalai, Jeanne C. Stachowiak

Producción científica: Articlerevisión exhaustiva

4 Citas (Scopus)


Cellular membranes, which are densely crowded by proteins, take on an elaborate array of highly curved shapes. Steric pressure generated by protein crowding plays a significant role in shaping membrane surfaces. It is increasingly clear that many proteins involved in membrane remodeling contain substantial regions of intrinsic disorder. These domains have large hydrodynamic radii, suggesting that they may contribute significantly to steric congestion on membrane surfaces. However, it has been unclear to what extent they are capable of generating steric pressure, owing to their conformational flexibility. To address this gap, we use a recently developed sensor based on Förster resonance energy transfer to measure steric pressure generated at membrane surfaces by the intrinsically disordered domain of the endocytic protein, AP180. We find that disordered domains generate substantial steric pressure that arises from both entropic and electrostatic components. Interestingly, this steric pressure is largely invariant with the molecular weight of the disordered domain, provided that coverage of the membrane surface is held constant. Moreover, equivalent levels of steric pressure result in equivalent degrees of membrane remodeling, regardless of protein molecular weight. This result, which is consistent with classical polymer scaling relationships for semi-dilute solutions, helps to explain the molecular and physical origins of steric pressure generation by intrinsically disordered domains. From a physiological perspective, these findings suggest that a broad range of membrane-associated disordered domains are likely to play a significant and previously unknown role in controlling membrane shape.

Idioma originalEnglish (US)
Páginas (desde-hasta)3320-3333
Número de páginas14
PublicaciónBiophysical Journal
EstadoPublished - sept 20 2022

ASJC Scopus subject areas

  • Biophysics


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