Structure of nucleoprotein MA: The 50S ribosomal subunit fromH. marismortuiX-ray crystallographic model of 29 of the 33 native components, from the laboratory ofThomas Steitz. Of the 31 component proteins, 27 are shown (blue), along with its 2 RNA strands (orange/yellow).[1] Scale: assembly is approx. 24 nm across.[2]
Inmolecular biology, the termmacromolecular assembly (MA) refers to massive chemical structures such asviruses and non-biologicnanoparticles, cellularorganelles andmembranes andribosomes, etc. that are complex mixtures ofpolypeptide,polynucleotide,polysaccharide or other polymericmacromolecules. They are generally of more than one of these types, and the mixtures are defined spatially (i.e., with regard to their chemical shape), and with regard to their underlying chemical composition andstructure. Macromolecules are found in living and nonliving things, and are composed of many hundreds or thousands ofatoms held together bycovalent bonds; they are often characterized by repeating units (i.e., they arepolymers). Assemblies of these can likewise be biologic or non-biologic, though the MA term is more commonly applied in biology, and the termsupramolecular assembly is more often applied in non-biologic contexts (e.g., insupramolecular chemistry andnanotechnology). MAs of macromolecules are held in their defined forms bynon-covalentintermolecular interactions (rather thancovalent bonds), and can be in either non-repeating structures (e.g., as in the ribosome (image) and cell membrane architectures), or in repeating linear, circular, spiral, or other patterns (e.g., as inactin filaments and theflagellar motor, image). The process by which MAs are formed has been termedmolecular self-assembly, a term especially applied in non-biologic contexts. A wide variety of physical/biophysical, chemical/biochemical, and computational methods exist for the study of MA; given the scale (molecular dimensions) of MAs, efforts to elaborate their composition and structure and discern mechanisms underlying their functions are at the forefront of modern structure science.
A eukaryoticribosome, which catalyticallytranslate the information content contained inmRNA molecules into proteins. The animation presents the elongation and membrane targeting stages ofeukaryotic translation, showing the mRNA as a black arc, theribosome subunits in green and yellow, tRNAs in dark blue, proteins such aselongation and other factors involved in light blue, the growing polypeptide chain as a black thread growing vertically from the curve of the mRNA. At end of the animation, the polypeptide produced is extruded through a light blue SecY pore[3] into the gray interior of theER.
3D printed model of the structure of abacterialflagellum "motor" and partial rod structure of aSalmonella species. Bottom to top: dark blue, repeating FliM and FliN, motor/switch proteins; red, FliG motor/switch proteins; yellow, FliF transmembrane coupling proteins; light blue, L and P ring proteins; and (at top), dark blue, the cap, hook-filament junction, hook, and rod proteins.[4]
Abiomolecular complex, also called abiomacromolecular complex, is any biological complex made of more than onebiopolymer (protein,RNA,DNA,[5]carbohydrate) or large non-polymeric biomolecules (lipid). The interactions between these biomolecules are non-covalent.[6]Examples:
Complexes of macromolecules occur ubiquitously in nature, where they are involved in the construction of viruses and all living cells. In addition, they play fundamental roles in all basic life processes (protein translation,cell division,vesicle trafficking, intra- and inter-cellular exchange of material between compartments, etc.). In each of these roles, complex mixtures of become organized in specific structural and spatial ways. While the individual macromolecules are held together by a combination of covalent bonds andintramolecular non-covalent forces (i.e., associations between parts within each molecule, viacharge-charge interactions,van der Waals forces, anddipole–dipole interactions such ashydrogen bonds), by definition MAs themselves are held together solely via thenoncovalent forces, except now exertedbetween molecules (i.e.,intermolecular interactions).[citation needed]
The images above give an indication of the compositions and scale (dimensions) associated with MAs, though these just begin to touch on the complexity of the structures; in principle, each living cell is composed of MAs, but is itself an MA as well. In the examples and other such complexes and assemblies, MAs are each often millions ofdaltons in molecular weight (megadaltons, i.e., millions of times the weight of a single, simple atom), though still having measurable component ratios (stoichiometries) at some level of precision. As alluded to in the image legends, when properly prepared, MAs or component subcomplexes of MAs can often be crystallized for study byprotein crystallography and related methods, or studied by other physical methods (e.g.,spectroscopy,microscopy).[citation needed]
Cross-sections of phospholipid (PLs) relevant tobiomembrane MAs. Yellow-orange indicateshydrophobic lipid tails; black and white spheres represent PL polar regions (v.i.). Bilayer/liposome dimensions (obscured in graphic): hydrophobic and polar regions, each ~30 Å (3.0 nm) "thick"—the polar from ~15 Å (1.5 nm)on each side.[11][12][13][non-primary source needed][14]A graphical representation of the structure of a viral MA,cowpea mosaic virus, with 30 copies of each of its coat proteins, the small coat protein (S, yellow) and the large coat protein (L, green), which, along with 2 molecules ofpositive-senseRNA (RNA-1 and RNA-2, not visible) constitute the virion. The assembly is highlysymmetric, and is ~280 Å (28 nm) across at its widest point.[verification needed][citation needed]
Virus structures were among the first studied MAs; other biologic examples include ribosomes (partial image above), proteasomes, and translation complexes (withprotein andnucleic acid components), procaryotic and eukaryotic transcription complexes, andnuclear and other biologicalpores that allow material passage between cells and cellular compartments.Biomembranes are also generally considered MAs, though the requirement for structural and spatial definition is modified to accommodate the inherentmolecular dynamics of membranelipids, and of proteins withinlipid bilayers.[15]
During assembly of thebacteriophage (phage) T4virion, the morphogenetic proteins encoded by the phagegenes interact with each other in a characteristic sequence. Maintaining an appropriate balance in the amounts of each of these proteins produced during viral infection appears to be critical for normal phage T4morphogenesis.[16] Phage T4 encoded proteins that determine virion structure include major structural components, minor structural components and non-structural proteins that catalyze specific steps in the morphogenesis sequence[17]
Finally, biology is not the sole domain of MAs. The fields ofsupramolecular chemistry andnanotechnology each have areas that have developed to elaborate and extend the principles first demonstrated in biologic MAs. Of particular interest in these areas has been elaborating the fundamental processes ofmolecular machines, and extending known machine designs to new types and processes.[citation needed]
^Russell RB, Alber F, Aloy P, Davis FP, Korkin D, Pichaud M, et al. (June 2004). "A structural perspective on protein-protein interactions".Current Opinion in Structural Biology.14 (3):313–324.doi:10.1016/j.sbi.2004.04.006.PMID15193311.
^Experimental system, dioleoylphosphatidylcholine bilayers. The hydrophobic hydrocarbon region of the lipid is ~30 Å (3.0 nm) as determined by a combination of neutron and X-ray scattering methods; likewise, the polar/interface region (glyceryl, phosphate, and headgroup moieties, with their combined hydration) is ~15 Å (1.5 nm)on each side, for a total thickness about equal to the hydrocarbon region. See S.H. White references, preceding and following.
^Hydrocarbon dimensions vary with temperature, mechanical stress, PL structure and coformulants, etc. by single- to low double-digit percentages of these values.[citation needed]
^Floor E (February 1970). "Interaction of morphogenetic genes of bacteriophage T4".Journal of Molecular Biology.47 (3):293–306.doi:10.1016/0022-2836(70)90303-7.PMID4907266.
^Snustad DP (August 1968). "Dominance interactions in Escherichia coli cells mixedly infected with bacteriophage T4D wild-type and amber mutants and their possible implications as to type of gene-product function: catalytic vs. stoichiometric".Virology.35 (4):550–63.doi:10.1016/0042-6822(68)90285-7.PMID4878023.
Williamson JR (August 2008). "Cooperativity in macromolecular assembly".Nature Chemical Biology.4 (8):458–465.doi:10.1038/nchembio.102.PMID18641626.
Perrakis A, Musacchio A, Cusack S, Petosa C (August 2011). "Investigating a macromolecular complex: the toolkit of methods".Journal of Structural Biology.175 (2):106–12.doi:10.1016/j.jsb.2011.05.014.PMID21620973.
Perino A, Ghigo A, Damilano F, Hirsch E (August 2006). "Identification of the macromolecular complex responsible for PI3Kgamma-dependent regulation of cAMP levels".Biochemical Society Transactions.34 (Pt 4):502–3.doi:10.1042/BST0340502.PMID16856844.
Barhoum S, Palit S, Yethiraj A (May 2016). "Diffusion NMR studies of macromolecular complex formation, crowding and confinement in soft materials".Progress in Nuclear Magnetic Resonance Spectroscopy.94–95:1–10.Bibcode:2016PNMRS..94....1B.doi:10.1016/j.pnmrs.2016.01.004.PMID27247282.
Nobel Prizes in Chemistry (2012), The Nobel Prize in Chemistry 2009, Venkatraman Ramakrishnan, Thomas A. Steitz, Ada E. Yonath,The Nobel Prize in Chemistry 2009, accessed 13 June 2011.
Nobel Prizes in Chemistry (2012), The Nobel Prize in Chemistry 1982, Aaron Klug,The Nobel Prize in Chemistry 1982, accessed 13 June 2011.
