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Centrosymmetric bilayers in the 0.75 Å resolution structure of a designed alpha-helical peptide, d,l-Alpha-1

Published online by Cambridge University Press:  01 July 1999

WILLIAM R. PATTERSON ,
DANIEL H. ANDERSON ,
WILLIAM F. DeGRADO ,
DUILIO CASCIO  and
DAVID EISENBERG
WILLIAM R. PATTERSON
Affiliation:
UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute at UCLA and the Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1570 Present address: TherOx, Inc., 2400 Michelson Dr., Irvine, California 92612.
DANIEL H. ANDERSON
Affiliation:
UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute at UCLA and the Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1570
WILLIAM F. DeGRADO
Affiliation:
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059
DUILIO CASCIO
Affiliation:
UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute at UCLA and the Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1570
DAVID EISENBERG
Affiliation:
UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Molecular Biology Institute at UCLA and the Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1570
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Abstract

We report the 0.75 Å crystal structure of a racemic mixture of the 12-residue designed peptide “Alpha-1” (Acetyl-ELLKKLLEELKG), the L-enantiomer of which is described in the accompanying paper. Equivalent solutions of the centrosymmetric bilayers were determined by two direct phasing programs in space groups P1 and P1. The unit cell contains two l-alpha-helices and two d-alpha-helices. The columnar-sheet bilayer motif seen in l-Alpha-1 is maintained in the d,l-Alpha-1 structure except that each sheet of head-to-tail helices is composed of one enantiomer and is related to its neighboring sheets by inversion symmetry. Comparison to the l-Alpha-1 structure provides further insight into peptide design. The high resolution and small asymmetric unit allowed building an intricate model (R = 13.1%, Rfree = 14.5%) that incorporates much of the discrete disorder of peptide and solvent. Ethanolamine and 2-methyl-2,4-pentanediol (MPD) molecules bind near helix termini. Rigid body analysis identifies sites of restricted displacements and torsions. Side-chain discrete disorder propagates into the backbone of one helix but not the other. Although no side chain in Alpha-1 is rigid, the environments in the crystal restrict some of them to no or only one active torsion.

Keywords

amphiphilic bilayeratomic resolutioncentrosymmetricdesigned peptiderigid body analysis
Type
Research Article
Information
Protein Science , Volume 8 , Issue 7 , July 1999 , pp. 1410 - 1422
Copyright
© 1999 The Protein Society

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