File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Crystal structure of a self-assembling lipopeptide detergent at 1.20 A

TitleCrystal structure of a self-assembling lipopeptide detergent at 1.20 A
Authors
Issue Date2008
Citation
Proceedings of the National Academy of Sciences, 2008, v. 105 n. 35, p. 12861-12866 How to Cite?
AbstractLipopeptide detergents (LPDs) are a new class of amphiphile designed specifically for the structural study of integral membrane proteins. The LPD monomer consists of a 25-residue peptide with fatty acyl chains linked to side chains located at positions 2 and 24 of the peptide. LPDs are designed to form alpha-helices that self-assemble into cylindrical micelles, providing a more natural interior acyl chain packing environment relative to traditional detergents. We have determined the crystal structure of LPD-12, an LPD coupled to two dodecanoic acids, to a resolution of 1.20 A. The LPD-12 monomers adopt the target conformation and associate into cylindrical octamers as expected. Pairs of helices are strongly associated as Alacoil-type antiparallel dimers, and four of these dimers interact through much looser contacts into assemblies with approximate D(2) symmetry. The aligned helices form a cylindrical shell with a hydrophilic exterior that protects an interior hydrophobic cavity containing the 16 LPD acyl chains. Over 90% of the methylene/methyl groups from the acylated side chains are visible in the micelle interiors, and approximately 90% of these adopt trans dihedral angle conformations. Dodecylmaltoside (DDM) was required for the crystallization of LPD-12, and we find 10-24 ordered DDM molecules associated with each LPD assembly, resulting in an overall micelle molecular weight of approximately 30 kDa. The structures confirm the major design objectives of the LPD framework, and reveal unexpected features that will be helpful in the engineering additional versions of lipopeptide amphiphiles.
Persistent Identifierhttp://hdl.handle.net/10722/130951
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Argonne National Laboratory
Structural Biology Center at the Advanced Photon Source
UChicago Argonne, LLC
U.S. Department of Energy
Office of Biological and Environmental ResearchDE-AC02-06CH11357
Funding Information:

ACKNOWLEDGMENTS. We thank Peter Tieleman for providing an implementation of the TWISTER algorithm. This work was supported by a grant from the Canadian Institutes of Health Research (to G.G.P.). D.N.H. was supported by a Canadian Institutes of Health Research Training Grant. Results shown in this report are derived from work performed at Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357.

 

DC FieldValueLanguage
dc.contributor.authorHo, DN-
dc.contributor.authorPomroy, NC-
dc.contributor.authorCuesta-Seijo, JAen_HK
dc.contributor.authorPrive, GGen_HK
dc.date.accessioned2011-01-11T04:17:09Z-
dc.date.available2011-01-11T04:17:09Z-
dc.date.issued2008-
dc.identifier.citationProceedings of the National Academy of Sciences, 2008, v. 105 n. 35, p. 12861-12866-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/130951-
dc.description.abstractLipopeptide detergents (LPDs) are a new class of amphiphile designed specifically for the structural study of integral membrane proteins. The LPD monomer consists of a 25-residue peptide with fatty acyl chains linked to side chains located at positions 2 and 24 of the peptide. LPDs are designed to form alpha-helices that self-assemble into cylindrical micelles, providing a more natural interior acyl chain packing environment relative to traditional detergents. We have determined the crystal structure of LPD-12, an LPD coupled to two dodecanoic acids, to a resolution of 1.20 A. The LPD-12 monomers adopt the target conformation and associate into cylindrical octamers as expected. Pairs of helices are strongly associated as Alacoil-type antiparallel dimers, and four of these dimers interact through much looser contacts into assemblies with approximate D(2) symmetry. The aligned helices form a cylindrical shell with a hydrophilic exterior that protects an interior hydrophobic cavity containing the 16 LPD acyl chains. Over 90% of the methylene/methyl groups from the acylated side chains are visible in the micelle interiors, and approximately 90% of these adopt trans dihedral angle conformations. Dodecylmaltoside (DDM) was required for the crystallization of LPD-12, and we find 10-24 ordered DDM molecules associated with each LPD assembly, resulting in an overall micelle molecular weight of approximately 30 kDa. The structures confirm the major design objectives of the LPD framework, and reveal unexpected features that will be helpful in the engineering additional versions of lipopeptide amphiphiles.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshCrystallography, X-Ray-
dc.subject.meshDetergents - chemistry-
dc.subject.meshLipids - chemistry-
dc.subject.meshPeptides - chemistry-
dc.titleCrystal structure of a self-assembling lipopeptide detergent at 1.20 Aen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=105&issue=35&spage=12861&epage=12866&date=2008&atitle=Crystal+structure+of+a+self-assembling+lipopeptide+detergent+at+1.20+A-
dc.identifier.emailHo, DN: hodona711@yahoo.com-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.0801941105-
dc.identifier.pmid18753631-
dc.identifier.pmcidPMC2529112-
dc.identifier.scopuseid_2-s2.0-51349125801-
dc.identifier.hkuros181535-
dc.identifier.volume105-
dc.identifier.issue35-
dc.identifier.spage12861-
dc.identifier.epage12866-
dc.identifier.isiWOS:000259343000045-
dc.identifier.f10001119480-
dc.identifier.citeulike3172391-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats