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The unique mechanism of SNX9 BAR domain for inducing membrane tubulation.

Park J, Zhao H, Chang S - Mol. Cells (2014)

Bottom Line: It has a Bin-Amphiphysin-Rvs (BAR) domain which can form a crescent-shaped homodimer structure that induces deformation of the plasma membrane.While other BAR-domain containing proteins such as amphiphysin and endophilin have an amphiphatic helix in front of the BAR domain which plays a critical role in membrane penetration, SNX9 does not.Thus, whether and how SNX9 BAR domain could induce the deformation of the plasma membrane is not clear.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea ; Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea.

ABSTRACT
Sorting nexin 9 (SNX9) is a member of the sorting nexin family of proteins and plays a critical role in clathrin-mediated endocytosis. It has a Bin-Amphiphysin-Rvs (BAR) domain which can form a crescent-shaped homodimer structure that induces deformation of the plasma membrane. While other BAR-domain containing proteins such as amphiphysin and endophilin have an amphiphatic helix in front of the BAR domain which plays a critical role in membrane penetration, SNX9 does not. Thus, whether and how SNX9 BAR domain could induce the deformation of the plasma membrane is not clear. The present study identified the internal putative amphiphatic stretch in the 1(st) α-helix of the SNX9 BAR domain and proved that together with the N-terminal helix (H0) region, this internal putative amphiphatic stretch is critical for inducing membrane tubulation. Therefore, our study shows that SNX9 uses a unique mechanism to induce the tubulation of the plasma membrane which mediates proper membrane deformation during clathrin-mediated endocytosis.

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Related in: MedlinePlus

SNX9 has a functional BAR domain. (A) SNX9 domain structure. Unlike N-BAR protein, endophilin, SNX9 has a C-terminal BAR domain. (B) Multiple sequence alignment of BAR domains in human SNX9 and rat endophilin A1. Conserved amino-acids residues are highlighted with black boxes. Secondary structure of them was determined from the crystal structure. An asterisk (*) indicate the amino-acid residues involved in the dimerization, which is related to BAR-BAR contacts. Symbols of consensus sequence are: 1, D/N; 2, E/Q; and 6, hydrophobic.
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f1-molcell-37-10-753: SNX9 has a functional BAR domain. (A) SNX9 domain structure. Unlike N-BAR protein, endophilin, SNX9 has a C-terminal BAR domain. (B) Multiple sequence alignment of BAR domains in human SNX9 and rat endophilin A1. Conserved amino-acids residues are highlighted with black boxes. Secondary structure of them was determined from the crystal structure. An asterisk (*) indicate the amino-acid residues involved in the dimerization, which is related to BAR-BAR contacts. Symbols of consensus sequence are: 1, D/N; 2, E/Q; and 6, hydrophobic.

Mentions: SNX9 is composed of four functional domains: N-terminal SH3, LC, PX, and C-terminal BAR domains (Fig. 1A). While other BAR domain-containing proteins such as amphiphysin and endophilin have the BAR domain in their N-terminus, the SNX9 BAR domain is located in its C-terminus. Figure 1B shows a multiple alignment of the human SNX9 BAR domain and rat endophilin A1 BAR domain. We found that in addition to the N-terminal short helix region (H0), SNX9 has additional insert region in the middle of helix1. This extra insert region is located in the middle of its membrane binding surface and contains hydro-phobic, acid and basic amino acids, which make it a putative amphiphatic region.


The unique mechanism of SNX9 BAR domain for inducing membrane tubulation.

Park J, Zhao H, Chang S - Mol. Cells (2014)

SNX9 has a functional BAR domain. (A) SNX9 domain structure. Unlike N-BAR protein, endophilin, SNX9 has a C-terminal BAR domain. (B) Multiple sequence alignment of BAR domains in human SNX9 and rat endophilin A1. Conserved amino-acids residues are highlighted with black boxes. Secondary structure of them was determined from the crystal structure. An asterisk (*) indicate the amino-acid residues involved in the dimerization, which is related to BAR-BAR contacts. Symbols of consensus sequence are: 1, D/N; 2, E/Q; and 6, hydrophobic.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4213767&req=5

f1-molcell-37-10-753: SNX9 has a functional BAR domain. (A) SNX9 domain structure. Unlike N-BAR protein, endophilin, SNX9 has a C-terminal BAR domain. (B) Multiple sequence alignment of BAR domains in human SNX9 and rat endophilin A1. Conserved amino-acids residues are highlighted with black boxes. Secondary structure of them was determined from the crystal structure. An asterisk (*) indicate the amino-acid residues involved in the dimerization, which is related to BAR-BAR contacts. Symbols of consensus sequence are: 1, D/N; 2, E/Q; and 6, hydrophobic.
Mentions: SNX9 is composed of four functional domains: N-terminal SH3, LC, PX, and C-terminal BAR domains (Fig. 1A). While other BAR domain-containing proteins such as amphiphysin and endophilin have the BAR domain in their N-terminus, the SNX9 BAR domain is located in its C-terminus. Figure 1B shows a multiple alignment of the human SNX9 BAR domain and rat endophilin A1 BAR domain. We found that in addition to the N-terminal short helix region (H0), SNX9 has additional insert region in the middle of helix1. This extra insert region is located in the middle of its membrane binding surface and contains hydro-phobic, acid and basic amino acids, which make it a putative amphiphatic region.

Bottom Line: It has a Bin-Amphiphysin-Rvs (BAR) domain which can form a crescent-shaped homodimer structure that induces deformation of the plasma membrane.While other BAR-domain containing proteins such as amphiphysin and endophilin have an amphiphatic helix in front of the BAR domain which plays a critical role in membrane penetration, SNX9 does not.Thus, whether and how SNX9 BAR domain could induce the deformation of the plasma membrane is not clear.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea ; Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea.

ABSTRACT
Sorting nexin 9 (SNX9) is a member of the sorting nexin family of proteins and plays a critical role in clathrin-mediated endocytosis. It has a Bin-Amphiphysin-Rvs (BAR) domain which can form a crescent-shaped homodimer structure that induces deformation of the plasma membrane. While other BAR-domain containing proteins such as amphiphysin and endophilin have an amphiphatic helix in front of the BAR domain which plays a critical role in membrane penetration, SNX9 does not. Thus, whether and how SNX9 BAR domain could induce the deformation of the plasma membrane is not clear. The present study identified the internal putative amphiphatic stretch in the 1(st) α-helix of the SNX9 BAR domain and proved that together with the N-terminal helix (H0) region, this internal putative amphiphatic stretch is critical for inducing membrane tubulation. Therefore, our study shows that SNX9 uses a unique mechanism to induce the tubulation of the plasma membrane which mediates proper membrane deformation during clathrin-mediated endocytosis.

Show MeSH
Related in: MedlinePlus