2e3r
From Proteopedia
| Line 2: | Line 2: | ||
caption="2e3r, resolution 1.65Å" /> | caption="2e3r, resolution 1.65Å" /> | ||
'''Crystal structure of CERT START domain in complex with C18-ceramide (P1)'''<br /> | '''Crystal structure of CERT START domain in complex with C18-ceramide (P1)'''<br /> | ||
| + | |||
| + | ==Overview== | ||
| + | In mammalian cells, ceramide is synthesized in the endoplasmic reticulum, and transferred to the Golgi apparatus for conversion to sphingomyelin., Ceramide transport occurs in a nonvesicular manner and is mediated by, CERT, a cytosolic 68-kDa protein with a C-terminal steroidogenic acute, regulatory protein-related lipid transfer (START) domain. The CERT START, domain efficiently transfers natural D-erythro-C16-ceramide, but not, lipids with longer (C20) amide-acyl chains. The molecular mechanisms of, ceramide specificity, both stereo-specific recognition and length limit, are not well understood. Here we report the crystal structures of the CERT, START domain in its apo-form and in complex with ceramides having, different acyl chain lengths. In these complex structures, one ceramide, molecule is buried in a long amphiphilic cavity. At the far end of the, cavity, the amide and hydroxyl groups of ceramide form a hydrogen bond, network with specific amino acid residues that play key roles in, stereo-specific ceramide recognition. At the head of the ceramide, molecule, there is no extra space to accommodate additional bulky groups., The two aliphatic chains of ceramide are surrounded by the hydrophobic, wall of the cavity, whose size and shape dictate the length limit for, cognate ceramides. Furthermore, local high-crystallographic B-factors, suggest that the alpha-3 and the Omega1 loop might work as a gate to, incorporate the ceramide into the cavity. Thus, the structures demonstrate, the structural basis for the mechanism by which CERT can distinguish, ceramide from other lipid types yet still recognize multiple species of, ceramides. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2E3R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=18C:'>18C</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E3R OCA]. | + | 2E3R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=18C:'>18C</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:18c+Binding+Site+For+Residue+A+1100'>AC1</scene> and <scene name='pdbsite=AC2:18c+Binding+Site+For+Residue+B+1200'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E3R OCA]. |
| + | |||
| + | ==Reference== | ||
| + | Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide., Kudo N, Kumagai K, Tomishige N, Yamaji T, Wakatsuki S, Nishijima M, Hanada K, Kato R, Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):488-93. Epub 2008 Jan 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18184806 18184806] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 19: | Line 25: | ||
[[Category: lipid transport]] | [[Category: lipid transport]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:17:07 2008'' |
Revision as of 06:17, 13 February 2008
|
Crystal structure of CERT START domain in complex with C18-ceramide (P1)
Overview
In mammalian cells, ceramide is synthesized in the endoplasmic reticulum, and transferred to the Golgi apparatus for conversion to sphingomyelin., Ceramide transport occurs in a nonvesicular manner and is mediated by, CERT, a cytosolic 68-kDa protein with a C-terminal steroidogenic acute, regulatory protein-related lipid transfer (START) domain. The CERT START, domain efficiently transfers natural D-erythro-C16-ceramide, but not, lipids with longer (C20) amide-acyl chains. The molecular mechanisms of, ceramide specificity, both stereo-specific recognition and length limit, are not well understood. Here we report the crystal structures of the CERT, START domain in its apo-form and in complex with ceramides having, different acyl chain lengths. In these complex structures, one ceramide, molecule is buried in a long amphiphilic cavity. At the far end of the, cavity, the amide and hydroxyl groups of ceramide form a hydrogen bond, network with specific amino acid residues that play key roles in, stereo-specific ceramide recognition. At the head of the ceramide, molecule, there is no extra space to accommodate additional bulky groups., The two aliphatic chains of ceramide are surrounded by the hydrophobic, wall of the cavity, whose size and shape dictate the length limit for, cognate ceramides. Furthermore, local high-crystallographic B-factors, suggest that the alpha-3 and the Omega1 loop might work as a gate to, incorporate the ceramide into the cavity. Thus, the structures demonstrate, the structural basis for the mechanism by which CERT can distinguish, ceramide from other lipid types yet still recognize multiple species of, ceramides.
About this Structure
2E3R is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide., Kudo N, Kumagai K, Tomishige N, Yamaji T, Wakatsuki S, Nishijima M, Hanada K, Kato R, Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):488-93. Epub 2008 Jan 9. PMID:18184806
Page seeded by OCA on Wed Feb 13 08:17:07 2008
