Structure of a lipid droplet protein; the PAT family member TIP47.
The perilipin/ADRP/TIP47 (PAT) proteins localize to the surface of intracellular neutral lipid droplets. Perilipin is essential for lipid storage and hormone regulated lipolysis in adipocytes, and perilipin null mice exhibit a dramatic reduction in adipocyte lipid stores. A significant fraction of the approximately 200 amino acid N-terminal region of the PAT proteins consists of 11-mer helical repeats that are also found in apolipoproteins and other lipid-associated proteins. The C-terminal 60% of TIP47, a representative PAT protein, comprises a monomeric and independently folded unit. The crystal structure of the C-terminal portion of TIP47 was determined and refined at 2.8 A resolution. The structure consists of an alpha/beta domain of novel topology and a four-helix bundle resembling the LDL receptor binding domain of apolipoprotein E. The structure suggests an analogy between PAT proteins and apolipoproteins in which helical repeats interact with lipid while the ordered C-terminal region is involved in protein:protein interactions.
Hickenbottom
Sabrina J
SJ
Laboratory of Cellular and Developmental Biology, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA.
Kimmel
Alan R
AR
Londos
Constantine
C
Hurley
James H
JH
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000070778:Perilipin-1; D000070780:Perilipin-2; D000070796:Perilipin-3; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D011257:Pregnancy Proteins / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; C038196:PLIN3 protein, human; D000070778:Perilipin-1; D000070780:Perilipin-2; D000070796:Perilipin-3; D010750:Phosphoproteins; C000602983:Plin2 protein, mouse; D011257:Pregnancy Proteins; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins