Assessment of conformation and energetics of the N-terminal part of elafin via computer simulations

被引:4
作者
Efremov, RG
Volynsky, PE
Dauchez, MAM
Nolde, DE
Arseniev, AS
Alix, AJP
机构
[1] Univ Reims, Fac Sci, Lab Spect & Struct Biomol, F-51687 Reims 2, France
[2] Russian Acad Sci, MM Shemyakin & Yu A Ovchinnikov Inst Bioorgan Che, Moscow 117871, Russia
关键词
peptide-membrane interactions; secondary structure; protein conformation; solvation potential; molecular modeling;
D O I
10.1007/s002140000237
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Elafin, a specific inhibitor of elastase, is thought to play a regulatory role in inflammation. An NMR-derived solution structure of recombinant elafin has been reported [Francart ct al. (1997) J Mol Biol 268:666 ], although the conformation of its flexible N-terminal part is not established. There is experimental evidence that the N terminus (residues 1-15) of elafin interacts with the cell membrane. To explore the conformational preferences of residues in this region, we have performed Monte Carlo simulations of the peptide in water, in cyclohexane, and in a model membrane. Additionally, 3.7-ns molecular dynamics with explicit water was carried out. The main results were that the hydrophobic environment stabilizes an alpha helix in the region 6-11, the peptide is unordered in water, and it is attached to the membrane via the amphiphilic alpha -helix 6-11, which inserts with its N terminus forming an angle of about 60 degrees to the membrane plane. We therefore assume that in nonpolar media the N-terminal part of elafin forms a short alpha helix which might act as a membrane anchor.
引用
收藏
页码:55 / 61
页数:7
相关论文
共 24 条
[1]  
Alix AJP, 1997, SPECTROSCOPY OF BIOLOGICAL MOLECULES: MODERN TRENDS, P23
[2]  
[Anonymous], 2000, RUSS J BIOORG CHEM+, DOI DOI 10.1007/BF02759157
[3]   STRUCTURAL BASIS OF AMINO-ACID ALPHA-HELIX PROPENSITY [J].
BLABER, M ;
ZHANG, XJ ;
MATTHEWS, BW .
SCIENCE, 1993, 260 (5114) :1637-1640
[4]   PEPTIDES IN MEMBRANES - HELICITY AND HYDROPHOBICITY [J].
DEBER, CM ;
LI, SC .
BIOPOLYMERS, 1995, 37 (05) :295-318
[5]   A solvent model for simulations of peptides in bilayers.: I.: Membrane-promoting α-helix formation [J].
Efremov, RG ;
Nolde, DE ;
Vergoten, G ;
Arseniev, AS .
BIOPHYSICAL JOURNAL, 1999, 76 (05) :2448-2459
[6]   ENVIRONMENTAL CHARACTERISTICS OF RESIDUES IN PROTEINS - 3-DIMENSIONAL MOLECULAR HYDROPHOBICITY POTENTIAL APPROACH [J].
EFREMOV, RG ;
ALIX, AJP .
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 1993, 11 (03) :483-507
[7]   APPLICATION OF 3-DIMENSIONAL MOLECULAR HYDROPHOBICITY POTENTIAL TO THE ANALYSIS OF SPATIAL-ORGANIZATION OF MEMBRANE DOMAINS IN PROTEINS .1. HYDROPHOBIC PROPERTIES OF TRANSMEMBRANE SEGMENTS OF NA+, K+-ATPASE [J].
EFREMOV, RG ;
GULYAEV, DI ;
VERGOTEN, G ;
MODYANOV, NN .
JOURNAL OF PROTEIN CHEMISTRY, 1992, 11 (06) :665-675
[8]   THE HYDROPHOBIC MOMENT DETECTS PERIODICITY IN PROTEIN HYDROPHOBICITY [J].
EISENBERG, D ;
WEISS, RM ;
TERWILLIGER, TC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (01) :140-144
[9]   Solution structure of r-elafin, a specific inhibitor of elastase [J].
Francart, C ;
Dauchez, M ;
Alix, AJP ;
Lippens, G .
JOURNAL OF MOLECULAR BIOLOGY, 1997, 268 (03) :666-677
[10]   COMPARISON OF ATOMIC SOLVATION PARAMETRIC SETS - APPLICABILITY AND LIMITATIONS IN PROTEIN-FOLDING AND BINDING [J].
JUFFER, AH ;
EISENHABER, F ;
HUBBARD, SJ ;
WALTHER, D ;
ARGOS, P .
PROTEIN SCIENCE, 1995, 4 (12) :2499-2509