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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.


Structure of human ALG-2. (A) The N-terminal region is rich in Ala/Gly/Pro. A penta-EF-hand (PEF) domain has five EF hands (EF1–EF5) with eight α-helices (α1–α8). An alternatively spliced isoform lacks two residues (Gly121Phe122); (B) X-ray crystal structure of the dimeric Ca2+-bound form of human ALG-2 (PDB code: 2ZN9) is presented by cartoon using PyMol. EF-hands are shown in different colors for each EF-hand module corresponding to EF1–EF5 in panel A. Gray spheres, calcium atoms.
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ijms-17-01401-f001: Structure of human ALG-2. (A) The N-terminal region is rich in Ala/Gly/Pro. A penta-EF-hand (PEF) domain has five EF hands (EF1–EF5) with eight α-helices (α1–α8). An alternatively spliced isoform lacks two residues (Gly121Phe122); (B) X-ray crystal structure of the dimeric Ca2+-bound form of human ALG-2 (PDB code: 2ZN9) is presented by cartoon using PyMol. EF-hands are shown in different colors for each EF-hand module corresponding to EF1–EF5 in panel A. Gray spheres, calcium atoms.

Mentions: Human ALG-2 (22 kDa, 191 amino acids) has an Ala/Gly/Pro/-rich N-terminal tail followed by a penta-EF-hand (PEF) domain (Figure 1), which is a region comprised of approximately 170 amino acid residues containing five repeated helix-loop-helix Ca2+-binding motifs (EF-hands) [13]. The PEF family includes ALG-2, peflin, sorcin, grancalcin, and calpain subfamily members in mammals [14]. Generally, a pair of EF-hands forms a discrete domain in Ca2+-binding proteins with even numbers of EF-hands [15]. Stabilization of the paired EF-hands is facilitated by hydrophobic interactions within two types of motifs (cluster I and cluster II), each comprised of three residues separately residing at the pairing partner EF-hands [16]. PEF proteins have a unique feature of utilizing the isolated fifth EF-hand (EF5) to pair with that of another PEF protein molecule to form a homodimer or heterodimer: ALG-2/ALG-2 [3,17] and ALG-2/peflin [18], sorcin/sorcin [19], grancalcin/grancalcin [20] and sorcin/grancalcin [21], and large and small subunits of typical calpains [22]. An alternatively spliced isoform lacking Gly121Phe122 is generated by utilization of an upstream splicing donor site in mouse and human pre-mRNAs [23,24] and is designated ALG-2ΔGF122 in this review article.


Multifaceted Roles of ALG-2 in Ca 2+ -Regulated Membrane Trafficking
Structure of human ALG-2. (A) The N-terminal region is rich in Ala/Gly/Pro. A penta-EF-hand (PEF) domain has five EF hands (EF1–EF5) with eight α-helices (α1–α8). An alternatively spliced isoform lacks two residues (Gly121Phe122); (B) X-ray crystal structure of the dimeric Ca2+-bound form of human ALG-2 (PDB code: 2ZN9) is presented by cartoon using PyMol. EF-hands are shown in different colors for each EF-hand module corresponding to EF1–EF5 in panel A. Gray spheres, calcium atoms.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5037681&req=5

ijms-17-01401-f001: Structure of human ALG-2. (A) The N-terminal region is rich in Ala/Gly/Pro. A penta-EF-hand (PEF) domain has five EF hands (EF1–EF5) with eight α-helices (α1–α8). An alternatively spliced isoform lacks two residues (Gly121Phe122); (B) X-ray crystal structure of the dimeric Ca2+-bound form of human ALG-2 (PDB code: 2ZN9) is presented by cartoon using PyMol. EF-hands are shown in different colors for each EF-hand module corresponding to EF1–EF5 in panel A. Gray spheres, calcium atoms.
Mentions: Human ALG-2 (22 kDa, 191 amino acids) has an Ala/Gly/Pro/-rich N-terminal tail followed by a penta-EF-hand (PEF) domain (Figure 1), which is a region comprised of approximately 170 amino acid residues containing five repeated helix-loop-helix Ca2+-binding motifs (EF-hands) [13]. The PEF family includes ALG-2, peflin, sorcin, grancalcin, and calpain subfamily members in mammals [14]. Generally, a pair of EF-hands forms a discrete domain in Ca2+-binding proteins with even numbers of EF-hands [15]. Stabilization of the paired EF-hands is facilitated by hydrophobic interactions within two types of motifs (cluster I and cluster II), each comprised of three residues separately residing at the pairing partner EF-hands [16]. PEF proteins have a unique feature of utilizing the isolated fifth EF-hand (EF5) to pair with that of another PEF protein molecule to form a homodimer or heterodimer: ALG-2/ALG-2 [3,17] and ALG-2/peflin [18], sorcin/sorcin [19], grancalcin/grancalcin [20] and sorcin/grancalcin [21], and large and small subunits of typical calpains [22]. An alternatively spliced isoform lacking Gly121Phe122 is generated by utilization of an upstream splicing donor site in mouse and human pre-mRNAs [23,24] and is designated ALG-2ΔGF122 in this review article.

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.