Principles of the Architecture and morphogenesis of biological Assemblies

Moet Hennessy-LouisVuitton (LVMH) Science for Art Prize Genesis of Forms: Part I-Biology and Biomimetism Created in 1988, theMoet Hennessy-Louis Vuitton (LVMH)ScienceforArt Prize annua18 rewardsartists and scientificresearchers from all ouer the worldfor thepotential impact oftheir discoverieson artistic or aestheticcreation . The 1996prize was awarded for workfalling under the theme “Genesisof Forms: Part I-Biology and Biomimetism.’’ In 1997 theprize will be awardedfm “Genesis of Forms:Part II-Mathematics, Physical and Earth Sciences.’’ Theprizes consist of twofirst prizes (an Art Prize and a Science Prize)and the Vinci ofExcellencefor scientific wmk ofthe highest international h e 1 (thesescientistsreached thefinal stage of the selectionprocess). See Leonard0 30, No. 3, 183-1 86for further information about theLVMH Sciencefor Art Prize. PRINCIPLES OF THE ARCHITECTURE AND MORPHOGENESIS OF BIOLOGICALASSEMBLIES Aaron Klug, Laboratory of Molecular Biology, Hills Road, CambridgeCB2 2QH, UnitedKingdom. The work reported in this Abstract was awarded the 1996LVMH Special Prize. Much of the fabric of a cell, including its internal skeleton, is built of arrays of large biological molecules such as proteins and polysaccharides. Similarly, the enzymatic and synthetic machinery within a cell consists primarily of such assemblies,which are sometimes so distinctive in form and function as to deserve the name organelle.The assemblies concerned with replication of the cell and its genetic component involve the nucleic acid polymers: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA),which form complexes with various sets of proteins. Methods over the last 30 to 40 yearsnotably X-ray diffraction and electron microscopy-have been developed for investigating these kinds of assemblies, so that precise information about their structures is possible, in some cases right down to molecular detail. This enables the study of chemical interactions between the structural units constituting these ordered biological systems. Complemented by biochemical studies allowing researchers to follow the path (orpaths) by which the systems are assembled out of their constituent units, the information about the assemblies’ structures allows us to begin to understand the chemical and physical principles underlying their formation. The key principle that runs through these systemsis the notion of specificity, which enables the different constituent molecules to recognize each other and exclude others that do not belong, so that no external instructions are necessary to form the assembly. In other words, the design of an ordered structure is built into the bonding properties of its constituents, so that the system “assemblesitself”without the need for a scaffold. a part in laying the foundations of this subject, which is now often called “structural molecular biology.” I shall not try to summarize here my work of more than 30 years to indicate all that we have learned from the different systems I have studied [11;rather, I will summarize key points of four systems. I have been privileged to have played The Structureand Assembly of Tobacco MosaicVirus Tobacco MosaicVirus (TMV) is the classic example of a simple virus whose rod shape results from its basic design -namely, a regular helical array of identical protein subunits, which has embedded in its framework a single molecule of RNA that carries its genetic information. The simple picture of assembly that might have been expected -namely, showing protein molecules attached to one another like steps in a spiral staircase, enclosing the RNA as a helical thread as the rods grow-is wrong in all essentials. The virus assembles in a much more complex way for good physical and biological reasons; in fact, the protein alone forms a two-layerdisc that is an obligatory intermediate in the assembly of the virus. This simultaneously fulfillsboth the physical requirement for nucleating the growth of the rod and the biological requirement for specific recognition of the viral RNA, allowing the rejection of foreign WAS. The Architecture of Spherical Viruses Many simple viruses are spherical in shape (Fig. l),with an outer shell made of protein units enclosing the RNA or DNA inside. One might have expected the shell to be built according to mathematical symmetry (point-groupsymmetry ) in which all units would be identically situated, making the same (equivalent) interactions with their neighbors. We discovered, however, that a number of viruses, including the polio virus, did in fact have icosahedral symmetry,yet we found that...