| Symbol: | VASt domain |
| VASt domain | |
| Pfam: | PF16016 |
| Interpro: | IPR031968 |
VAD1 analog of StAR-related lipid transfer (VASt) is a steroidogenic acute regulatory protein‐related lipid transfer (StART)-like lipid-binding domain first identified in the vad1 (vascular associated death1) protein in Arabidopsis thaliana (mouse-ear cress).[1] [2] Proteins containing these domains are found in eukaryotes and usually contain another lipid-binding domain, typically the GRAM domain and sometimes the C2 domain in plants and the integral peroxisomal membrane peroxin Pex24p domain in oomycetes.[1]
The VASt domain structurally resembles a truncated form of a START domain, but with limited sequence similarity.[1] [3] While VASt is a member of the Bet v1-like superfamily, it is unclear if it evolved from the same ancestral domain as the START domain or is an example of convergent evolution.[1]
The domain is highly conserved across all eukaryotes and is typically present in only one copy in VASt domain-containing proteins.[1] Like the START domain, the VASt domain consists of a helix-grip fold structure. The pocket formed is large enough to bind one lipid such as cholesterol,[4] 25-hydroxycholesterol[5] or ergosterol.[2] [3]
Analysis of the crystal structure of unbound and bound forms of VASt domains in lipid transfer proteins anchored at a membrane contact site (LAMs) from yeast revealed that the domain contains an accessible hydrophobic cavity."[3] [5] Upon sterol binding of the cavity, the entry point is closed or partially closed to the outside.
The sole proteins containing this domain identified in human are GRAMD1A/Aster-A, GRAMD1B/Aster-B and GRAMD1C/Aster-C (with the VASt domain referred to as an Aster domain[4]). These sterol transfer proteins together with GRAMD2A and GRAMD2B are LAM family proteins, although the latter two lack the VASt domain.[6] Like LAM proteins, GRAMD1 proteins preferentially transfer sterols.[3] [4]