Biology:Gram domain containing 1a

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Short description: Protein that is encoded by the GRAMD1A gene


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


GRAM domain containing 1A also known as Aster-A is a protein that is encoded by the GRAMD1A gene. [1][2] It contains a transmembrane region, a GRAM domain and a VASt domain that can bind cholesterol.[3][4] GRAMD1A has four paralogs: GRAMD1B and GRAMD1C and two without VASt domains, GRAMD2A and GRAMD2B. These proteins are mammalian representatives of the yeast lipid transfer proteins anchored at a membrane contact site (LAM) family.[3]

The protein is expressed ubiquitously with higher levels in the central nervous system.[5]

Function

GRAMD1A localizes to the endoplasmic reticulum.[3] Its GRAM domain tethers it to the plasma membrane where it can bind phosphatidylinositol phosphate in areas enriched for it.[3][6]

When the plasma membrane contains high levels of cholesterol, GRAMD1a like GRAMD1b and GRAMD1c moves to sites of contact between the plasma membrane and the endoplasmic reticulum.[4] The VASt domain of GRAMD1A then binds cholesterol and cholesterol is moved from the plasma membrane to the endoplasmic reticulum.[4][7] The VASt domain is responsible for binding cholesterol while the GRAM domain determines the location of the protein through sensing of cholesterol and binding partially negatively charged lipids in the plasma membrane, especially phosphatidylserine.[4][8]

GRAMD1A also is necessary for autophagosome biogenesis.[7]

References

  1. ↑ "Entrez Gene: GRAM domain containing 1A". https://www.ncbi.nlm.nih.gov/gene/57655. Retrieved 2017-09-15. 
  2. ↑ "UniProtKB - Q8VEF1 (ASTRA_MOUSE)". https://www.uniprot.org/uniprot/Q8VEF1. Retrieved March 6, 2020. 
  3. ↑ 3.0 3.1 3.2 3.3 "GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells". eLife 22 (7): e31019. February 2018. doi:10.7554/eLife.31019. PMID 29469807. 
  4. ↑ 4.0 4.1 4.2 4.3 "Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells". Cell 175 (2): 514–529.e20. October 2018. doi:10.1016/j.cell.2018.08.033. PMID 30220461. 
  5. ↑ "GRAMD1-mediated accessible cholesterol sensing and transport". Biochim Biophys Acta Mol Cell Biol Lipids 1866 (8): 158957. August 2021. doi:10.1016/j.bbalip.2021.158957. PMID 33932585. 
  6. ↑ "Toward the role of cholesterol and cholesterol transfer protein in autophagosome biogenesis". Autophagy 15 (12): 2167–2168. December 2019. doi:10.1080/15548627.2019.1666595. PMID 31512558. 
  7. ↑ 7.0 7.1 "The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis". Nat. Chem. Biol. 15 (7): 710–720. July 2019. doi:10.1038/s41589-019-0307-5. PMID 31222192. https://backend.orbit.dtu.dk/ws/files/218854172/FULLTEXT01.pdf. 
  8. ↑ "Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b". The EMBO Journal 40 (6): e106524. 19 February 2021. doi:10.15252/embj.2020106524. PMID 33604931. 

Further reading




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