Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101

VPS37 Isoforms Differentially Modulate the Ternary Complex Formation of ALIX, ALG-2, and ESCRT-I

“…13) We confirmed that the binding of ALIX to ESCRT-I isocomplex B depends on Ca 2þ and ALG-2 using purified ESCRT-I isocomplex B (Supplemental Fig. S1).…”

“…13) Based on the results obtained in this study, we propose a new model in which ALG-2 bridges the ESCRT-I complex and ALIX via interactions not only with TSG101 but also with VPS37. Furthermore, ESCRT-I complexes containing VPS37B or VPS37C subunits appear to have higher affinity for ALG-2 in the presence of Ca 2þ , and this might increase the affinity of these ESCRT-I complexes for ALIX (Fig.…”

“…-tagged VPS28, TSG101, VPS37B, VPS37C, VPS37D, MVB12A, and MVB12B, GFPfused mammalian expression vectors for humanVPS28 iso1, VPS37A, TSG101, TSG101 PRR , and ALIX and Strep-tagged ALG-2 were described previously. 13,17,18) To construct an expression vector for Myc-tagged VPS37A, a cDNA fragment encoding VPS37A was amplified by PCR with a set of specific primers (Supplemental Table S1, see Biosci. Biotechnol.…”

“…It interacts with both ALIX and TSG101 in the presence of Ca 2þ and acts as a Ca 2þ -dependent adaptor protein bridging the two proteins. 13,14) Our recent screening of proline-rich proteins as potential novel ALG-2-binding partners revealed that the PRR of VPS37C interacts with ALG-2. 15) Thus TSG101 might not be the only ESCRT-I subunit capable of binding to ALG-2.…”

Mammalian ESCRT-III-Related Protein IST1 Has a Distinctive Met-Pro Repeat Sequence That Is Essential for Interaction with ALG-2 in the Presence of Ca2+

“…[13][14][15] Although ALIX has a binding site for TSG101, we have reported that the weak ALIX-TSG101 interaction is potentiated by ALG-2, which bridges the two proteins and functions as a Ca 2þ -dependent adaptor protein. 16) The currently known interaction network of ESCRTs, ALIX, and ALG-2 is shown in Supplemental Fig. S1 (see Biosci.…”