Model-based analysis of assembly kinetics for virus capsids or other spherical polymers

被引:197
作者
Endres, D
Zlotnick, A
机构
[1] Univ Cent Oklahoma, Dept Math & Stat, Edmond, OK 73034 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA
基金
美国国家科学基金会;
关键词
D O I
10.1016/S0006-3495(02)75245-4
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
The assembly of virus capsids or other spherical polymers-empty, closed structures composed of hundreds of protein subunits-is poorly understood. Assembly of a closed spherical polymer is unlike polymerization of a filament or crystal, examples of open-ended polymers. This must be considered to develop physically meaningful analyses. We have developed a model of capsid assembly, based on a cascade of low-order reactions, that allows us to calculate kinetic simulations. The behavior of this model resembles assembly kinetics observed in solution (Zlotnick, A., J. M. Johnson, P. W. Wingfield, S. J. Stahl, and D. Endres. 1999. Biochemistry. 38:14644-14652). We exhibit two examples of this general model describing assembly of dodecahedral and icosahedral capsids. Using simulations based on these examples, we demonstrate how to extract robust estimates of assembly parameters from accessible experimental data. These parameters, nucleus size, average nucleation rate, and average free energy of association can be determined from measurement of subunit and capsid as time and concentration vary. Mathematical derivations of the analyses, carried out for a general model, are provided in an Appendix. The understanding of capsid assembly developed in this paper is general; the examples provided can be readily modified to reflect different biological systems. This enhanced understanding of virus assembly will allow a more quantitative analysis of virus stability and biological or antiviral factors that affect assembly.
引用
收藏
页码:1217 / 1230
页数:14
相关论文
共 33 条
[1]   ASSEMBLY OF A SPHERICAL PLANT-VIRUS [J].
ADOLPH, KW ;
BUTLER, PJG .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES, 1976, 276 (943) :113-&
[2]   FORMATION OF AN INFECTIOUS NUCLEOPROTEIN FROM PROTEIN AND NUCLEIC ACID ISOLATED FROM A SMALL SPHERICAL VIRUS [J].
BANCROFT, JB ;
HIEBERT, E .
VIROLOGY, 1967, 32 (02) :354-&
[3]   SELF-ASSEMBLY OF A NUCLEIC-ACID FREE PSEUDO-TOP COMPONENT FOR A SMALL SPHERICAL VIRUS [J].
BANCROFT, JB ;
WAGNER, GW ;
BRACKER, CE .
VIROLOGY, 1968, 36 (01) :146-&
[4]   EFFECTS OF VARIOUS POLYANIONS ON SHELL FORMATION OF SOME SPHERICAL VIRUSES [J].
BANCROFT, JB ;
HIEBERT, E ;
BRACKER, CE .
VIROLOGY, 1969, 39 (04) :924-&
[5]   A STUDY OF SELF-ASSEMBLY PROCESS IN A SMALL SPHERICAL VIRUS - FORMATION OF ORGANIZED STRUCTURES FROM PROTEIN SUBUNITS IN VITRO [J].
BANCROFT, JB ;
HILLS, GJ ;
MARKHAM, R .
VIROLOGY, 1967, 31 (02) :354-&
[6]   HEPADNAVIRAL ASSEMBLY IS INITIATED BY POLYMERASE BINDING TO THE ENCAPSIDATION SIGNAL IN THE VIRAL-RNA GENOME [J].
BARTENSCHLAGER, R ;
SCHALLER, H .
EMBO JOURNAL, 1992, 11 (09) :3413-3420
[7]   ROLE AND MECHANISM OF THE MATURATION CLEAVAGE OF VPO IN POLIOVIRUS ASSEMBLY - STRUCTURE OF THE EMPTY CAPSID ASSEMBLY INTERMEDIATE AT 2.9-ANGSTROM RESOLUTION [J].
BASAVAPPA, R ;
SYED, R ;
FLORE, O ;
ICENOGLE, JP ;
FILMAN, DJ ;
HOGLE, JM .
PROTEIN SCIENCE, 1994, 3 (10) :1651-1669
[8]   ROLES OF OPERATOR AND NON-OPERATOR RNA SEQUENCES IN BACTERIOPHAGE R17 CAPSID ASSEMBLY [J].
BECKETT, D ;
WU, HN ;
UHLENBECK, OC .
JOURNAL OF MOLECULAR BIOLOGY, 1988, 204 (04) :939-947
[9]   LOCAL RULE-BASED THEORY OF VIRUS SHELL ASSEMBLY [J].
BERGER, B ;
SHOR, PW ;
TUCKERKELLOGG, L ;
KING, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7732-7736
[10]   PHYSICAL PRINCIPLES IN CONSTRUCTION OF REGULAR VIRUSES [J].
CASPAR, DLD ;
KLUG, A .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1962, 27 :1-&