A review of multi-domain and flexible molecular chaperones studies by small-angle X-ray scattering

被引：21
作者：
Borges J.C. [1 ]
Seraphim T.V. [1 ]
Dores-Silva P.R. [1 ]
Barbosa L.R.S. [2 ]
机构：
[1] Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP
[2] Instituto de Física, Universidade de São Paulo, São Paulo, SP
来源：
Biophysical Reviews | 2016年 / 8卷 / 2期
关键词：
Molecular chaperones; Mortalin Hsp70; Multi-domain proteins; Protein dynamics; SAXS;
D O I：
10.1007/s12551-016-0194-x
中图分类号：
学科分类号：
摘要：
Intrinsic flexibility is closely related to protein function, and a plethora of important regulatory proteins have been found to be flexible, multi-domain or even intrinsically disordered. On the one hand, understanding such systems depends on how these proteins behave in solution. On the other, small-angle X-ray scattering (SAXS) is a technique that fulfills the requirements to study protein structure and dynamics relatively quickly with few experimental limitations. Molecular chaperones from Hsp70 and Hsp90 families are multi-domain proteins containing flexible and/or disordered regions that play central roles in cellular proteostasis. Here, we review the structure and function of these proteins by SAXS. Our general approach includes the use of SAXS data to determine size and shape parameters, as well as protein shape reconstruction and their validation by using accessory biophysical tools. Some remarkable examples are presented that exemplify the potential of the SAXS technique. Protein structure can be determined in solution even at limiting protein concentrations (for example, human mortalin, a mitochondrial Hsp70 chaperone). The protein organization, flexibility and function (for example, the J-protein co-chaperones), oligomeric status, domain organization, and flexibility (for the Hsp90 chaperone and the Hip and Hep1 co-chaperones) may also be determined. Lastly, the shape, structural conservation, and protein dynamics (for the Hsp90 chaperone and both p23 and Aha1 co-chaperones) may be studied by SAXS. We believe this review will enhance the application of the SAXS technique to the study of the molecular chaperones. © 2016, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg.
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页码：107 / 120
页数：13
相关论文
共 152 条
[91]  
Onuoha S.C., Couistock E.T., Grossmann J.G., Jackson S.E., Structural studies on the co-chaperone Hop and its complexes with Hsp90, J Mol Biol, 379, pp. 732-744, (2008)
[92]  
Ortore M.G., Spinozzi F., Mariani P., Paciaroni A., Barbosa L.R., Amenitsch H., Steinhart M., Ollivier J., Russo D., Combining structure and dynamics: non-denaturing high-pressure effect on lysozyme in solution, J R Soc Interface, 6, pp. S619-S634, (2009)
[93]  
Pallavi R., Roy N., Nageshan R.K., Talukdar P., Pavithra S.R., Reddy R., Venketesh S., Kumar R., Gupta A.K., Singh R.K., Yadav S.C., Tatu U., Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug, J Biol Chem, 285, pp. 37964-37975, (2010)
[94]  
Panaretou B., Prodromou C., Roe S.M., O'Brien R., Ladbury J.E., Piper P.W., Pearl L.H., ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo, EMBO J, 17, pp. 4829-4836, (1998)
[95]  
Panaretou B., Siligardi G., Meyer P., Maloney A., Sullivan J.K., Singh S., Millson S.H., Clarke P.A., Naaby-Hansen S., Stein R., Cramer R., Mollapour M., Workman P., Piper P.W., Pearl L.H., Prodromou C., Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1, Mol Cell, 10, pp. 1307-1318, (2002)
[96]  
Partridge J.R., Lavery L.A., Elnatan D., Naber N., Cooke R., Agard D.A., A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity, eLife 3, (2014)
[97]  
Patki J.M., Pawar S.S., HSP90: chaperone-me-not, Pathol Oncol Res, 19, pp. 631-640, (2013)
[98]  
Pierpaoli E.V., Sandmeier E., Schonfeld H.J., Christen P., Control of the DnaK chaperone cycle by substoichiometric concentrations of the co-chaperones DnaJ and GrpE, J Biol Chem, 273, pp. 6643-6649, (1998)
[99]  
Pullen L., Bolon D.N., Enforced N-domain proximity stimulates Hsp90 ATPase activity and is compatible with function in vivo, J Biol Chem, 286, pp. 11091-11098, (2011)
[100]  
Putnam C.D., Hammel M., Hura G.L., Tainer J.A., X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution, Q Rev Biophys, 40, pp. 191-285, (2007)
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