Conditional peripheral membrane proteins: facing up to limited specificity

Structure. 2012 Jan 11;20(1):15-27. doi: 10.1016/j.str.2011.11.012. Epub 2011 Dec 21.


Regulated relocalization of signaling and trafficking proteins is crucial for the control of many cellular processes and is driven by a series of domains that respond to alterations at membrane surfaces. The first examples of these domains--conditional peripheral membrane proteins--included C1, C2, PH, PX, and FYVE domains, which specifically recognize single tightly regulated membrane components such as diacylglycerol or phosphoinositides. The structural basis for this recognition is now well understood. Efforts to identify additional domains with similar functions that bind other targets (or participate in unexplained cellular processes) have not yielded many more examples of specific phospholipid-binding domains. Instead, most of the recently discovered conditional peripheral membrane proteins bind multiple targets (each with limited specificity), relying on coincidence detection and/or recognizing broader physical properties of the membrane such as charge or curvature. This broader range of recognition modes presents significant methodological challenges for a full structural understanding.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Membrane / metabolism
  • Membrane Lipids / metabolism*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Models, Molecular*
  • Protein Binding*
  • Protein Structure, Tertiary*


  • Membrane Lipids
  • Membrane Proteins