Article 2: Membrane Curvature

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Uses of Membrane Curvature

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Eukaryote's survivability is highly dependent on shapes of membranes. Membrane curvature play roles in shaping organelles, facilitating scission or fusion between two membrane leaflets, facilitating vesicle tethering, sorting proteins into different regions of the membrane, and activating proteins.[1]

Proteins can Induce Membrane Curvature

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Some biologically occurring lipids do exhibit spontaneous curvature which could explain the shapes of biological membranes. Nevertheless, calculations show that spontaneous lipid curvature alone is either insufficient or would require conditions that are unrealistic to drive the degree of curvature observed in most cells. It is now known that lipid curvature is "aided" by protein structures in order to generate complete cellular curvature.

Currently there are 4 proposed mechanisms to explain protein-mediated membrane bending:

  1. Lipid Clustering
  2. Protein forms rigid scaffold
  3. Insertion of amphipathic domains
  4. Protein Crowding

Lipid Clustering

Bacterial toxins such as cholera toxin B, shiga toxin B favors binding and thus clustering of certain lipid molecules. The effect of lipid clustering, together with the intrinsic shape of individual lipid molecule, give rise to membrane curvature.[1]

Protein Forms Rigid Scaffold

A classical example of membrane bending by rigid protein scaffold is clathrin. Clathrin is involved in cellular endocytosis and is sequestrated by specific signaling molecules. Clathrin can attach to adaptor protein complexes on the cellular membrane, and it polymerizes into lattices to drive greater curvature, resulting in endocytosis of a vesicular unit. Coat protein complex I (COP1) and coat protein complex II (COPII) follow similar mechanism in driving membrane curvature.[2] Figure A shows a protein coating that induces curvature. As mentioned above, proteins such as clathrin are recruited to the membrane through signaling molecules and assemble into larger polymeric structures that form a rigid structure which serves as a frame for the membrane. Clathrin binds to its receptors that are present in the membrane.

Another example of protein interactions that directly affect membrane curvature is that of the BAR (Bin, amphiphysin, Rvs’) domain. The BAR domain is present in a large family of proteins. Relative to the cellular lipid bilayer, this domain is rigid and exhibits a "banana" shape. It has been postulated that the positively charged amino acid residues in the concave region of the BAR domain would come into contact with the negatively charged polar head groups of lipids in the bilayer, thus allows the binding process.[3] Upon binding, the membrane's curvature is increased by the rigid domain.[4] Figure B shows bending of membrane by banana-shape like BAR domain.

Insertion of Hydrophobic Protein Motifs

Hydrophobic portion of protein can act as "wedge" when inserting into lipid bilayer. Epsin is one example that utilizes this mechanism to drive membrane bending. Epsin has several amphipathic alpha helices that allows it to partition between the hydrophobic core of the membrane and surrounding aqueous, hydrophilic environment. Another interesting characteristic of epsin and other proteins that bind to membranes is the fact that it shows high binding affinity for a fairly common membrane lipid, phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2)[5]. Unlike other proteins that simply bend the membrane through sheer rigidity, epsin is a globular soluble protein and thus not rigid. The insertion of its helices into the membrane force the neighboring lipids of the leaflet that has been bound to expand laterally. This displacement of lipids on only one of the leaflets increases the bilayer's curvature. Figure C shows membrane bending by insertion of hydrophobic protein parts into lipid bilayer.

Mechanisms of curvature induction by proteins
This figure illustrates membrane bending caused by protein crowding. When a high local concentration of proteins (shown in green) are present on membrane surface (shown in black), membrane curvature can be induced. This hypothesis reasoned that the high protein concentration increases the likelihood of repulsions between proteins, therefore generates steric pressure between proteins. To relieve such pressure, lipid membrane has to bend in order to decrease protein repulsions.

Protein Crowding

The protein crowding mechanism hypothesizes that proteins can bend membrane without directly perturbing membrane structures like the above mechanisms. When a high enough local concentration of protein is present on membrane surface, repulsion between protein molecules on the membrane surface can induce membrane curvature[6]. Although contribution of this mechanism remains unclear, multiple experimental and computation evidences have shown the its potential in bending membrane. A recent study even shows that protein crowding can cause membrane bending and leads to membrane fission[7][8]. These studies suggest that high local protein concentration can overcome the energy barrier to bend lipid membrane, and thus can contribute to membrane bending.

References

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  1. ^ a b McMahon, Harvey T.; Boucrot, Emmanuel (2015-03-15). "Membrane curvature at a glance". J Cell Sci. 128 (6): 1065–1070. doi:10.1242/jcs.114454. ISSN 0021-9533. PMC 4359918. PMID 25774051.{{cite journal}}: CS1 maint: PMC format (link)
  2. ^ Prinz WA, Hinshaw JE (2009-09-25). "Membrane-bending proteins". Critical Reviews in Biochemistry and Molecular Biology. 44 (5): 278–91. doi:10.1080/10409230903183472. PMC 3490495. PMID 19780639.
  3. ^ Zimmerberg J, McLaughlin S (March 2004). "Membrane curvature: how BAR domains bend bilayers". Current Biology. 14 (6): R250–2. doi:10.1016/j.cub.2004.02.060. PMID 15043839.
  4. ^ Martens S, McMahon HT (July 2008). "Mechanisms of membrane fusion: disparate players and common principles". Nature Reviews. Molecular Cell Biology. 9 (7): 543–56. doi:10.1038/nrm2417. PMID 18496517.
  5. ^ Stahelin RV, Long F, Peter BJ, Murray D, De Camilli P, McMahon HT, Cho W (August 2003). "Contrasting membrane interaction mechanisms of AP180 N-terminal homology (ANTH) and epsin N-terminal homology (ENTH) domains". The Journal of Biological Chemistry. 278 (31): 28993–9. doi:10.1074/jbc.M302865200. PMID 12740367.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ Guigas, Gernot; Weiss, Matthias (2016-10). "Effects of protein crowding on membrane systems". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1858 (10): 2441–2450. doi:10.1016/j.bbamem.2015.12.021. ISSN 0005-2736. {{cite journal}}: Check date values in: |date= (help)
  7. ^ Snead, Wilton T.; Hayden, Carl C.; Gadok, Avinash K.; Zhao, Chi; Lafer, Eileen M.; Rangamani, Padmini; Stachowiak, Jeanne C. (2017-04-18). "Membrane fission by protein crowding". Proceedings of the National Academy of Sciences. 114 (16): E3258–E3267. doi:10.1073/pnas.1616199114. ISSN 0027-8424. PMC 5402459. PMID 28373566.{{cite journal}}: CS1 maint: PMC format (link)
  8. ^ "UT researchers discover unknown mechanism of membrane fission". www.bmes.org. Retrieved 2018-09-03.