Title : Crystal structure of the conserved
domain of the DC lysosomal associated membrane
protein : implications for the lysosomal glycocalyx
Abstract :
- BACKGROUND: The family of lysosome-associated membrane proteins ( LAMP ) comprises the multifunctional, ubiquitous LAMP-1 and LAMP-2 , and the cell type-specific proteins DC-LAMP ( LAMP-3 ), BAD-LAMP ( UNC-46 , C20orf103 ) and macrosialin ( CD68 )
- LAMPs have been implicated in a multitude of cellular processes, including phagocytosis, autophagy, lipid transport and aging
- LAMP-2 isoform A acts as a receptor in chaperone-mediated autophagy
- LAMP LAMP-2 deficiency causes the fatal Danon disease
- The abundant proteins LAMP-1 and LAMP-2 are major constituents of the glycoconjugate coat present on the inside of the lysosomal membrane, the 'lysosomal glycocalyx'
- The LAMP family is characterized by a conserved domain of 150 to 200 amino acids with two disulfide bonds
- RESULTS: The crystal structure of the conserved domain of human DC-LAMP was solved
- It is the first high-resolution structure of a heavily glycosylated lysosomal membrane protein
- The structure represents a novel β-prism fold formed by two β-sheets bent by β-bulges and connected by a disulfide bond
- Flexible loops and a hydrophobic pocket represent possible sites of molecular interaction
- Computational models of the glycosylated luminal regions of LAMP-1 and LAMP-2 indicate that the proteins adopt a compact conformation in close proximity to the lysosomal membrane
- The models correspond to the thickness of the lysosomal glycoprotein coat of only 5 to 12 nm, according to electron microscopy
- CONCLUSION: The conserved luminal domain of lysosome-associated membrane proteins forms a previously unknown β-prism fold
- Insights into the structure of the lysosomal glycoprotein coat were obtained by computational models of the LAMP-1 and LAMP-2 luminal regions
Output (sent_index, trigger,
protein,
sugar,
site):
- 11. glycosylated, , -, -, regions
- 12. glycoprotein, , glycoprotein, -, -
- 14. glycoprotein, , glycoprotein, -, -
- 8. glycosylated, , glycosylated lysosomal membrane protein, -, -
Output(Part-Of) (sent_index,
protein,
site):
- 0. protein, domain
- 11. LAMP-1, regions
- 11. LAMP-2, regions
- 13. proteins, domain
- 14. LAMP-1, regions
- 14. LAMP-2, regions
- 7. DC-LAMP, domain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):