The membrane-proximal tryptophan-rich region of the HIV glycoprotein, gp41, forms a well-defined helix in dodecylphosphocholine micelles

被引:156
作者
Schibli, DJ
Montelaro, RC
Vogel, HJ
机构
[1] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada
[2] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA
关键词
D O I
10.1021/bi010640u
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The membrane-proximal tryptophan-rich region of the HIV transmembrane glycoprotein, gp41, plays an important role in the membrane fusion reaction. Using NMR spectroscopy, we have studied the tertiary structure of a synthetic 19-residue amidated peptide (NH2-KWASLWNWFNITNWLWYIK-CONH2) corresponding to this region in membrane-mimetic environments. Initial experiments in sodium dodecyl sulfate/H2O micelles and trifluoroethanol gave poor results, because of low solubility. However, in dodecylphosphocholine micelles, we obtained excellent 500 and 800 MHz NMR spectra, suggesting that the peptide has a preference for a zwitterionic membrane-like environment. The final NMR structures demonstrated a well-defined helical peptide with a backbone rmsd of 0.47 +/- 0.18 Angstrom. Four of the five tryptophan residues. as well as the tyrosine residue, formed a "collar" of aromatic residues along the axial length of the helix. By analogy to related tryptophan-rich antimicrobial peptides, the structure indicates that the aromatic residues of the HIV peptide are positioned within the membrane-water interface of a phospholipid bilayer. This is confirmed by the observation of direct NOEs between the aromatic residues of the peptide to the headgroup and interfacial protons of prototonated dodecylphosphocholine. The bulk of the polar residues are positioned on one face of this structure, with the hydrophobic phenylalanine side chain on the opposing face, forming an amphipathic structure. This work shows that the Trp-rich membrane-proximal region of HIV and related viruses can bind to the surfaces of zwitterioninc membranes in a "Velcro-like" manner.
引用
收藏
页码:9570 / 9578
页数:9
相关论文
共 69 条
[1]   Interactions of the HIV-1 fusion peptide with large unilamellar vesicles and monolayers.: A cryo-TEM and spectroscopic study [J].
Agirre, A ;
Flach, C ;
Goñi, FM ;
Mendelsohn, R ;
Valpuesta, JM ;
Wu, FJ ;
Nieva, JL .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2000, 1467 (01) :153-164
[2]   Membrane fusion mediated by coiled coils: A hypothesis [J].
Bentz, J .
BIOPHYSICAL JOURNAL, 2000, 78 (02) :886-900
[3]   Dodecylphosphocholine micelles as a membrane like environment:: new results from NMR relaxation and paramagnetic relaxation enhancement analysis [J].
Beswick, V ;
Guerois, R ;
Cordier-Ochsenbein, F ;
Coïc, YM ;
Huynh-Dinh, T ;
Tostain, J ;
Noël, JP ;
Sanson, A ;
Neumann, JM .
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 1998, 28 (01) :48-58
[4]   Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].
Brunger, AT ;
Adams, PD ;
Clore, GM ;
DeLano, WL ;
Gros, P ;
Grosse-Kunstleve, RW ;
Jiang, JS ;
Kuszewski, J ;
Nilges, M ;
Pannu, NS ;
Read, RJ ;
Rice, LM ;
Simonson, T ;
Warren, GL .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921
[5]   STRUCTURE OF INFLUENZA HEMAGGLUTININ AT THE PH OF MEMBRANE-FUSION [J].
BULLOUGH, PA ;
HUGHSON, FM ;
SKEHEL, JJ ;
WILEY, DC .
NATURE, 1994, 371 (6492) :37-43
[6]   Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41 [J].
Caffrey, M ;
Cai, ML ;
Kaufman, J ;
Stahl, SJ ;
Wingfield, PT ;
Covell, DG ;
Gronenborn, AM ;
Clore, GM .
EMBO JOURNAL, 1998, 17 (16) :4572-4584
[7]   Simple, distortion-free homonuclear spectra of peptides and nucleic acids in water using excitation sculpting [J].
Callihan, D ;
West, J ;
Kumar, S ;
Schweitzer, BI ;
Logan, TM .
JOURNAL OF MAGNETIC RESONANCE SERIES B, 1996, 112 (01) :82-85
[8]   Core structure of gp41 from the HIV envelope glycoprotein [J].
Chan, DC ;
Fass, D ;
Berger, JM ;
Kim, PS .
CELL, 1997, 89 (02) :263-273
[9]   HIV entry and its inhibition [J].
Chan, DC ;
Kim, PS .
CELL, 1998, 93 (05) :681-684
[10]   The amino-terminal fusion domain peptide of human immunodeficiency virus type 1 gp41 inserts into the sodium dodecyl sulfate micelle primarily as helix with a conserved glycine at the micelle-water interface [J].
Chang, DK ;
Cheng, SF ;
Chien, WJ .
JOURNAL OF VIROLOGY, 1997, 71 (09) :6593-6602