macromolecular assembly

File:Physical model of a bacterial flagellum.jpg model of the structure of a bacterial flagellum "motor" and partial rod structure of a Salmonella 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.Legend, cover art, J. Bacteriol., October 2006.{{full citation needed|date=October 2019}}]]

A biomolecular complex, also called a biomacromolecular complex, is any biological complex made of more than one biopolymer (protein, RNA, DNA,

{{cite journal | vauthors = Kleinjung J, Fraternali F | title = POPSCOMP: an automated interaction analysis of biomolecular complexes | journal = Nucleic Acids Research | volume = 33 | issue = Web Server issue | pages = W342–W346 | date = July 2005 | pmid = 15980485 | pmc = 1160130 | doi = 10.1093/nar/gki369 }}

carbohydrate) or large non-polymeric biomolecules (lipid). The interactions between these biomolecules are non-covalent.

{{cite journal | vauthors = Moore PB | title = How should we think about the ribosome? | journal = Annual Review of Biophysics | volume = 41 | issue = 1 | pages = 1–19 | date = 2012 | pmid = 22577819 | doi = 10.1146/annurev-biophys-050511-102314 }}

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, spliceosome, vault, SnRNP. Such complexes in cell nucleus are called ribonucleoproteins (RNPs).
• DNA-protein complexes: nucleosome.
• Protein-lipid complexes: lipoprotein.

{{cite journal | vauthors = Neuman N | title = The Complex Macromolecular Complex | journal = Trends in Biochemical Sciences | volume = 41 | issue = 1 | pages = 1–3 | date = January 2016 | pmid = 26699226 | doi = 10.1016/j.tibs.2015.11.006 | doi-access = free }}

{{cite journal | vauthors = Dutta S, Berman HM | title = Large macromolecular complexes in the Protein Data Bank: a status report | journal = Structure | volume = 13 | issue = 3 | pages = 381–388 | date = March 2005 | pmid = 15766539 | doi = 10.1016/j.str.2005.01.008 | doi-access = free }}

The biomacromolecular complexes are studied structurally by X-ray crystallography, NMR spectroscopy of proteins, cryo-electron microscopy and successive single particle analysis, and electron tomography.

{{cite journal | vauthors = Russell RB, Alber F, Aloy P, Davis FP, Korkin D, Pichaud M, Topf M, Sali A | display-authors = 6 | title = A structural perspective on protein-protein interactions | journal = Current Opinion in Structural Biology | volume = 14 | issue = 3 | pages = 313–324 | date = June 2004 | pmid = 15193311 | doi = 10.1016/j.sbi.2004.04.006 }}

The atomic structure models obtained by X-ray crystallography and biomolecular NMR spectroscopy can be 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.

{{cite journal | vauthors = van Dijk AD, Boelens R, Bonvin AM | title = Data-driven docking for the study of biomolecular complexes | journal = The FEBS Journal | volume = 272 | issue = 2 | pages = 293–312 | date = January 2005 | pmid = 15654870 | doi = 10.1111/j.1742-4658.2004.04473.x | hdl-access = free | s2cid = 20148856 | hdl = 1874/336958 }}

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 and intramolecular 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 forces, except now exerted between molecules (i.e., intermolecular interactions).{{citation needed|date=March 2019}}

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 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).{{citation needed|date=May 2020}}

File:Phospholipids aqueous solution structures.svg MAs. Yellow-orange indicates hydrophobic 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.{{cite web|url=http://blanco.biomol.uci.edu/Bilayer_Struc.html |title=Structure of Fluid Lipid Bilayers |publisher=Blanco.biomol.uci.edu |date=2009-11-10 |access-date=2019-10-09}}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.{{cite journal | vauthors = Wiener MC, White SH | title = Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. III. Complete structure | journal = Biophysical Journal | volume = 61 | issue = 2 | pages = 434–447 | date = February 1992 | pmid = 1547331 | pmc = 1260259 | doi = 10.1016/S0006-3495(92)81849-0 | bibcode = 1992BpJ....61..434W }}{{primary source inline|date=October 2019}}Hydrocarbon dimensions vary with temperature, mechanical stress, PL structure and coformulants, etc. by single- to low double-digit percentages of these values.{{citation needed|date=October 2019}}]]

File:CowpeaMosaicVirus3D.png, 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 positive-sense RNA (RNA-1 and RNA-2, not visible) constitute the virion. The assembly is highly symmetric, and is ~280 Å (28 nm) across at its widest point.{{verification needed|date=October 2019}}{{citation needed|date=October 2019}}]]

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 and other biological 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.{{cite journal | vauthors = Gerle C | title = Essay on Biomembrane Structure | journal = The Journal of Membrane Biology | volume = 252 | issue = 2–3 | pages = 115–130 | date = June 2019 | pmid = 30877332 | pmc = 6556169 | doi = 10.1007/s00232-019-00061-w }}

During assembly of the bacteriophage (phage) T4 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.{{cite journal | vauthors = Floor E | title = Interaction of morphogenetic genes of bacteriophage T4 | journal = Journal of Molecular Biology | volume = 47 | issue = 3 | pages = 293–306 | date = February 1970 | pmid = 4907266 | doi = 10.1016/0022-2836(70)90303-7 }} 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{{cite journal | vauthors = Snustad DP | title = 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 | journal = Virology | volume = 35 | issue = 4 | pages = 550–63 | date = August 1968 | pmid = 4878023 | doi = 10.1016/0042-6822(68)90285-7 }}

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.{{cite web |title=The Nobel Prize in Chemistry 2009 |url=https://www.nobelprize.org/prizes/chemistry/2009/summary/ |website=The Nobel Prize |publisher=Nobel Prize Outreach AB 2021 |access-date=10 May 2021}}

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.{{citation needed|date=May 2020}}

• 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

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{{Biological organisation}}

Category:Molecular biology

Category:Biochemistry