macromolecular assemblies
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X-ray crystallographic
X-ray crystallographic
model of 29 of the 33 native components, from the laboratory of Thomas Steitz. Of the 31 component proteins, 27 are shown (blue), along with its 2 RNA strands (orange/yellow). Scale: assembly is approx. 24 nm across. The term macromolecular assembly (MA) refers to massive chemical structures such as
virus A virus is a submicroscopic infectious agent that Viral replication, replicates only inside the living Cell (biology), cells of an organism. Viruses infect all types of life forms, from animals and plants to microorganisms, including bacte ...

virus
es and non-biologic
nanoparticle A nanoparticle or ultrafine particle is usually defined as a particle of matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched ...

nanoparticle
s, cellular
organelle In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...
s and
membranes Image:Schematic size.jpg, up150px, Schematic of size-based membrane exclusion A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membr ...

membranes
and
ribosome Ribosomes ( ), also called Palade granules, are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids t ...

ribosome
s, etc. that are complex mixtures of
polypeptide Peptides (from Greek language Greek (modern , romanized: ''Elliniká'', Ancient Greek, ancient , ''Hellēnikḗ'') is an independent branch of the Indo-European languages, Indo-European family of languages, native to Greece, Cyprus, Albania, o ...
,
polynucleotide A polynucleotide molecule is a biopolymer Biopolymers are natural polymers produced by the cells of Organism, living organisms. Biopolymers consist of monomeric units that are Covalent_bond, covalently bonded to form larger molecules. There are th ...
,
polysaccharide , a beta-glucan is an example of a (1→4)-β-D-glucan composed of glucose Glucose is a simple sugar with the Chemical formula#Molecular formula, molecular formula . Glucose is the most abundant monosaccharide, a subcategory of carbohydrates. Gl ...
or other polymeric
macromolecule macromolecule A macromolecule is a very large molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically neu ...
s. 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 and
structure A structure is an arrangement and organization of interrelated elements in a material object or system A system is a group of Interaction, interacting or interrelated elements that act according to a set of rules to form a unified whole. A ...
.
Macromolecule macromolecule A macromolecule is a very large molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically neu ...
s are found in living and nonliving things, and are composed of many hundreds or thousands of
atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ultimately composed of atom ...

atom
s held together by
covalent bond A covalent bond is a chemical bond that involves the sharing of electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs, and the stable balance of attractive and repulsive forces between atoms, when they sh ...
s; they are often characterized by repeating units (i.e., they are
polymers A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance or material consisting of very large molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of line ...

polymers
). Assemblies of these can likewise be biologic or non-biologic, though the MA term is more commonly applied in biology, and the term
supramolecular assembly thumbnail, Circular helicate 9+,_where_L_stands_for_s_tris-bpy_ligand_strand;_the_central_gray_atom_is_Cl,_while_the_smaller_gray_spheres_are_Fe..html" ;"title="Fe5L5)Clsup>9+, where L stands for s tris-bpy ligand strand; the central gray atom is ...
is more often applied in non-biologic contexts (e.g., in supramolecular chemistry and nanotechnology). MAs of macromolecules are held in their defined forms by non-covalent intermolecular interactions (rather than covalent bonds), and can be in either non-repeating structures (e.g., as in the
ribosome Ribosomes ( ), also called Palade granules, are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids t ...

ribosome
(image) and cell membrane architectures), or in repeating linear, circular, spiral, or other patterns (e.g., as in actin filaments and the flagellum, flagellar motor, image). The process by which MAs are formed has been termed molecular 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. Image:Protein translation.gif, 300px, A eukaryotic
ribosome Ribosomes ( ), also called Palade granules, are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids t ...

ribosome
, which catalytically translation (biology), translate the information content contained in mRNA molecules into proteins. The animation presents the elongation and membrane targeting stages of eukaryotic translation, showing the mRNA as a black arc, the
ribosome Ribosomes ( ), also called Palade granules, are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids t ...

ribosome
subunits in green and yellow, tRNAs in dark blue, proteins such as elongation factors, elongation 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 into the gray interior of the endoplasmic reticulum, ER.


Biomolecular complex

A biomolecular complex, also called a biomacromolecular complex, is any biological complex made of more than one biopolymer (protein, RNA, DNA, carbohydrate) or large non-polymeric biomolecules (lipid). The interactions between these biomolecules are non-covalent. Examples: * Protein complexes, some of which are multienzyme complexes: proteasome, DNA polymerase III holoenzyme, RNA polymerase II holoenzyme, symmetric viral capsids, chaperonin complex GroEL-GroES, photosystem I, ATP synthase, ferritin. * RNA-protein complexes:
ribosome Ribosomes ( ), also called Palade granules, are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids t ...

ribosome
, spliceosome, vault (organelle), vault, SnRNP. Such complexes in cell nucleus are called ribonucleoproteins (RNPs). * DNA-protein complexes: nucleosome. * Protein-lipid complexes: lipoprotein. The biomacromolecular complexes are studied structurally by X-ray crystallography, Nuclear magnetic resonance spectroscopy of proteins, NMR spectroscopy of proteins, cryo-electron microscopy and successive single particle analysis, and electron tomography. The atomic structure models obtained by X-ray crystallography and biomolecular NMR spectroscopy can be Macromolecular docking, docked into the much larger structures of biomolecular complexes obtained by lower resolution techniques like electron microscopy, electron tomography, and small-angle X-ray scattering. 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 (translation (biology), 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 and ''intra''molecular non-covalent forces (i.e., associations between parts within each molecule, via charge-charge interactions, van der Waals forces, and dipole-dipole interactions such as hydrogen bonds), by definition MAs themselves are held together solely via the noncovalent bonding, noncovalent forces, except now exerted ''between'' molecules (i.e., intermolecular interactions).


MA scales and examples

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 of dalton (unit), daltons 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 by protein crystallography and related methods, or studied by other physical methods (e.g., spectroscopy, microscopy). File:CowpeaMosaicVirus3D.png, 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 of Sense (molecular biology), positive-sense RNA (RNA-1 and RNA-2, not visible) constitute the virion. The assembly is highly symmetry, symmetric, and is ~280 Å (28 nm) across at its widest point. Virus structures were among the first studied MAs; other biologic examples include ribosomes (partial image above), proteasomes, and translation complexes (with protein and nucleic acid components), procaryotic and eukaryotic transcription complexes, and nuclear pore, nuclear and other biological wiktionary:pore, pores 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 inherent molecular dynamics of membrane lipids, and of proteins within lipid bilayers.


Virus assembly

During assembly of the Escherichia virus T4 , bacteriophage (phage) T4 virus, virion, the morphogenetic proteins encoded by the phage genes 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 T4 morphogenesis. 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


Research into MAs

The study of MA structure and function is challenging, in particular because of their megadalton size, but also because of their complex compositions and varying dynamic natures. Most have had standard chemical and biochemical methods applied (methods of protein purification and centrifugation, chemical and electrochemical characterization, etc.). In addition, their methods of study include modern proteomic approaches, computational and atomic-resolution structural methods (e.g., X-ray crystallography), small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), force spectroscopy, and transmission electron microscopy and cryo-electron microscopy. Aaron Klug was recognized with the 1982 Nobel Prize in Chemistry for his work on structural elucidation using electron microscopy, in particular for protein-nucleic acid MAs including the tobacco mosaic virus (a structure containing a 6400 base ssRNA molecule and >2000 coat protein molecules). The crystallization and structure solution for the ribosome, MW ~ 2.5 MDa, an example of part of the protein synthetic 'machinery' of living cells, was object of the 2009 Nobel Prize in Chemistry awarded to Venkatraman Ramakrishnan, Thomas A. Steitz, and Ada E. Yonath.


Non-biologic counterparts

Finally, biology is not the sole domain of MAs. The fields of supramolecular chemistry and nanotechnology 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 of molecular machines, and extending known machine designs to new types and processes.


See also

* Multi-state modeling of biomolecules * Quaternary structure * Multiprotein complex * Organelle: the broadest definition of "organelle" includes not only membrane bound cellular structures, but also very large biomolecular complexes. * Multi-state modeling of biomolecules


References


Further reading


General reviews

* * Perrakis A, Musacchio A, Cusack S, Petosa C. Investigating a macromolecular complex: the toolkit of methods. J Struct Biol. 2011 Aug;175(2):106-12. doi: 10.1016/j.jsb.2011.05.014. Epub 2011 May 18. Review. PubMed PMID: 21620973. * Dafforn TR. So how do you know you have a macromolecular complex? Acta Crystallogr D Biol Crystallogr. 2007 Jan;63(Pt 1):17-25. Epub 2006 Dec 13. Review. PubMed PMID: 17164522; PubMed Central PMCID: PMC2483502. * Wohlgemuth I, Lenz C, Urlaub H. Studying macromolecular complex stoichiometries by peptide-based mass spectrometry. Proteomics. 2015 Mar;15(5-6):862-79. doi: 10.1002/pmic.201400466. Epub 2015 Feb 6. Review. PubMed PMID: 25546807; PubMed Central PMCID: PMC5024058. * Sinha C, Arora K, Moon CS, Yarlagadda S, Woodrooffe K, Naren AP. Förster resonance energy transfer—An approach to visualize the spatiotemporal regulation of macromolecular complex formation and compartmentalized cell signaling. Biochim Biophys Acta. 2014 Oct;1840(10):3067-72. doi: 10.1016/j.bbagen.2014.07.015. Epub 2014 Jul 30. Review. PubMed PMID: 25086255; PubMed Central PMCID: PMC4151567. * and , ''Biochemistry.'' (W. H. Freeman and Company, 2002), * and , ''Lehninger Principles of Biochemistry.'' (Palgrave Macmillan, 2004),


Reviews on particular MAs

* Valle M. Almost lost in translation. Cryo-EM of a dynamic macromolecular complex: the ribosome. Eur Biophys J. 2011 May;40(5):589-97. doi: 10.1007/s00249-011-0683-6. Epub 2011 Feb 19. Review. PubMed PMID: 21336521. * Monie TP. The Canonical Inflammasome: A Macromolecular Complex Driving Inflammation. Subcell Biochem. 2017;83:43-73. doi: 10.1007/978-3-319-46503-6_2. Review. PubMed PMID: 28271472. * Perino A, Ghigo A, Damilano F, Hirsch E. Identification of the macromolecular complex responsible for PI3Kgamma-dependent regulation of cAMP levels. Biochem Soc Trans. 2006 Aug;34(Pt 4):502-3. Review. PubMed PMID: 16856844.


Primary sources

* * * Barhoum S, Palit S, Yethiraj A. Diffusion NMR studies of macromolecular complex formation, crowding and confinement in soft materials. Prog Nucl Magn Reson Spectrosc. 2016 May;94-95:1-10. doi: 10.1016/j.pnmrs.2016.01.004. Epub 2016 Feb 4. Review. PubMed PMID: 27247282.


Other sources

* 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

accessed 13 June 2011.


External links

*Beck Group (2019), Structure and function of large macromolecular assemblies (Beck group home page)
Beck Group - Structure and function of large molecular assemblies - EMBL
accessed 13 June 2011. *DMA Group (2019), Dynamics of macromolecular assembly (DMA Group home page)
Dynamics of Macromolecular Assembly Section , National Institute of Biomedical Imaging and Bioengineering
accessed 13 June 2011. {{Biological organisation Molecular biology Biochemistry