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Multifaceted Roles of ALG-2 in Ca 2+ -Regulated Membrane Trafficking

View Article: PubMed Central - PubMed

ABSTRACT

ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca2+-binding protein and interacts with a variety of proteins in a Ca2+-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca2+-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins.

No MeSH data available.


Different hydrophobic pockets used for the binding of ALG-2 to ALIX (ALG-2-interacting protein X) and Sec31A: (A) complex between ALG-2 and the ALIX peptide (PDB code, 2ZNE, chains A and C); and (B) complex between ALG-2 and the Sec31A peptide (PDB code, 3WXA, chains A and C). Peptides are shown in a stick model. Figures were taken from Ref. [58] and modified.
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ijms-17-01401-f002: Different hydrophobic pockets used for the binding of ALG-2 to ALIX (ALG-2-interacting protein X) and Sec31A: (A) complex between ALG-2 and the ALIX peptide (PDB code, 2ZNE, chains A and C); and (B) complex between ALG-2 and the Sec31A peptide (PDB code, 3WXA, chains A and C). Peptides are shown in a stick model. Figures were taken from Ref. [58] and modified.

Mentions: ALG-2-interacting proteins are classified into two major groups by structural features: (i) proteins containing binding sites in Pro-rich regions (PRRs) and (ii) proteins containing no obvious PRRs. By successfully narrowing down the binding sites in ALIX, PLSCR3 (phospholipid scramblase 3), and Sec31A, two different binding motifs were predicted [30,31,40,41]. Synthetic oligopeptides were used for X-ray crystallographic analyses of the ALG-2/oligopeptide complexes for ALIX and Sec31A in the presence of Zn2+ in place of Ca2+ [28,58]. While the ALIX peptide binds ALG-2 at two adjacent hydrophobic pockets largely formed by residues from EF3 to EF5 as well as by Y180 (EF5) of a dimerizing molecule (Pocket 1, PPYP) and from EF2 to EF4 (Pocket 2, YP), the Sec31A peptide binds at a different pocket largely formed by residues from EF1 to EF3 (Pocket 3, PPPPGFI) (Figure 2).


Multifaceted Roles of ALG-2 in Ca 2+ -Regulated Membrane Trafficking
Different hydrophobic pockets used for the binding of ALG-2 to ALIX (ALG-2-interacting protein X) and Sec31A: (A) complex between ALG-2 and the ALIX peptide (PDB code, 2ZNE, chains A and C); and (B) complex between ALG-2 and the Sec31A peptide (PDB code, 3WXA, chains A and C). Peptides are shown in a stick model. Figures were taken from Ref. [58] and modified.
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Related In: Results  -  Collection

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ijms-17-01401-f002: Different hydrophobic pockets used for the binding of ALG-2 to ALIX (ALG-2-interacting protein X) and Sec31A: (A) complex between ALG-2 and the ALIX peptide (PDB code, 2ZNE, chains A and C); and (B) complex between ALG-2 and the Sec31A peptide (PDB code, 3WXA, chains A and C). Peptides are shown in a stick model. Figures were taken from Ref. [58] and modified.
Mentions: ALG-2-interacting proteins are classified into two major groups by structural features: (i) proteins containing binding sites in Pro-rich regions (PRRs) and (ii) proteins containing no obvious PRRs. By successfully narrowing down the binding sites in ALIX, PLSCR3 (phospholipid scramblase 3), and Sec31A, two different binding motifs were predicted [30,31,40,41]. Synthetic oligopeptides were used for X-ray crystallographic analyses of the ALG-2/oligopeptide complexes for ALIX and Sec31A in the presence of Zn2+ in place of Ca2+ [28,58]. While the ALIX peptide binds ALG-2 at two adjacent hydrophobic pockets largely formed by residues from EF3 to EF5 as well as by Y180 (EF5) of a dimerizing molecule (Pocket 1, PPYP) and from EF2 to EF4 (Pocket 2, YP), the Sec31A peptide binds at a different pocket largely formed by residues from EF1 to EF3 (Pocket 3, PPPPGFI) (Figure 2).

View Article: PubMed Central - PubMed

ABSTRACT

ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca2+-binding protein and interacts with a variety of proteins in a Ca2+-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca2+-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins.

No MeSH data available.