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

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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.


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Subnetwork of ALG-2 and interacting proteins in the ESCRT system. Physical links are indicated by double-headed arrows colored in red for PEF proteins and in black for non-PEF proteins and lysobisphosphatidic acid (LBPA), a phospholipid enriched in MVB. Sites of phosphorylation by cytokinetic kinases are highlighted in green, and the TSG101 (tumor susceptibility gene 101) docking site is underlined in ALIX. Sequences of proteins containing the LYPXnL-motif and interacting with the V domain of ALIX are highlighted in cyan at the conserved residues. PRR, Pro-rich region. CEP55, centrosomal protein of 55 kDa; PLK1, Polo-like kinase 1; PKD, protein kinase D. The mode of interaction between ALG-2 and Sorcin is different from between ALG-2 and Ca2+-dependent targets (see Text).
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ijms-17-01401-f006: Subnetwork of ALG-2 and interacting proteins in the ESCRT system. Physical links are indicated by double-headed arrows colored in red for PEF proteins and in black for non-PEF proteins and lysobisphosphatidic acid (LBPA), a phospholipid enriched in MVB. Sites of phosphorylation by cytokinetic kinases are highlighted in green, and the TSG101 (tumor susceptibility gene 101) docking site is underlined in ALIX. Sequences of proteins containing the LYPXnL-motif and interacting with the V domain of ALIX are highlighted in cyan at the conserved residues. PRR, Pro-rich region. CEP55, centrosomal protein of 55 kDa; PLK1, Polo-like kinase 1; PKD, protein kinase D. The mode of interaction between ALG-2 and Sorcin is different from between ALG-2 and Ca2+-dependent targets (see Text).

Mentions: The ALG-2-interacting protein X, ALIX, has three distinct domains: N-terminal Bro1 domain, middle V domain and C-terminal Pro-rich region (PRR) (Figure 6). CHMP4 (ESCRT-III core subunit) and TSG101 (ESCRT-I subunit) bind ALIX at the Bro1 domain and the PRR, respectively. The V domain binds the so-called late domain of HIV (human immunodeficiency virus)-1 p6 Gag and EIAV (equine infectious anaemia virus) Gag p9 by recognizing the LYPXnL motif (Figure 6) [7,8,61]. Thus, ALIX promotes budding of retrovirus particles by bridging ESCRT-I and ESCRT-III. The V domain plays roles in cargo recognition by binding to the YPXnL motif of G protein-coupled receptor PAR1 and P2Y1 for ubiquitin-independent MVB sorting [62,63]. Binding of the ALIX V domain to polyubiquitin has also been reported [64].


Multifaceted Roles of ALG-2 in Ca 2+ -Regulated Membrane Trafficking
Subnetwork of ALG-2 and interacting proteins in the ESCRT system. Physical links are indicated by double-headed arrows colored in red for PEF proteins and in black for non-PEF proteins and lysobisphosphatidic acid (LBPA), a phospholipid enriched in MVB. Sites of phosphorylation by cytokinetic kinases are highlighted in green, and the TSG101 (tumor susceptibility gene 101) docking site is underlined in ALIX. Sequences of proteins containing the LYPXnL-motif and interacting with the V domain of ALIX are highlighted in cyan at the conserved residues. PRR, Pro-rich region. CEP55, centrosomal protein of 55 kDa; PLK1, Polo-like kinase 1; PKD, protein kinase D. The mode of interaction between ALG-2 and Sorcin is different from between ALG-2 and Ca2+-dependent targets (see Text).
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Related In: Results  -  Collection

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ijms-17-01401-f006: Subnetwork of ALG-2 and interacting proteins in the ESCRT system. Physical links are indicated by double-headed arrows colored in red for PEF proteins and in black for non-PEF proteins and lysobisphosphatidic acid (LBPA), a phospholipid enriched in MVB. Sites of phosphorylation by cytokinetic kinases are highlighted in green, and the TSG101 (tumor susceptibility gene 101) docking site is underlined in ALIX. Sequences of proteins containing the LYPXnL-motif and interacting with the V domain of ALIX are highlighted in cyan at the conserved residues. PRR, Pro-rich region. CEP55, centrosomal protein of 55 kDa; PLK1, Polo-like kinase 1; PKD, protein kinase D. The mode of interaction between ALG-2 and Sorcin is different from between ALG-2 and Ca2+-dependent targets (see Text).
Mentions: The ALG-2-interacting protein X, ALIX, has three distinct domains: N-terminal Bro1 domain, middle V domain and C-terminal Pro-rich region (PRR) (Figure 6). CHMP4 (ESCRT-III core subunit) and TSG101 (ESCRT-I subunit) bind ALIX at the Bro1 domain and the PRR, respectively. The V domain binds the so-called late domain of HIV (human immunodeficiency virus)-1 p6 Gag and EIAV (equine infectious anaemia virus) Gag p9 by recognizing the LYPXnL motif (Figure 6) [7,8,61]. Thus, ALIX promotes budding of retrovirus particles by bridging ESCRT-I and ESCRT-III. The V domain plays roles in cargo recognition by binding to the YPXnL motif of G protein-coupled receptor PAR1 and P2Y1 for ubiquitin-independent MVB sorting [62,63]. Binding of the ALIX V domain to polyubiquitin has also been reported [64].

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.


Related in: MedlinePlus