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.
引用
收藏
页码：107 / 120
页数：13
相关论文
共 152 条
[51]  
Hu J.B., Wu Y.K., Li J.Z., Qian X.G., Fu Z.Q., Sha B.D., The crystal structure of the putative peptide-binding fragment from the human Hsp40 protein Hdj1, BMC Struct Biol, 8, (2008)
[52]  
Hura G.L., Et al., Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS), Nat Methods, 6, pp. 606-612, (2009)
[53]  
Jacques D.A., Trewhella J., Small-angle scattering for structural biology-expanding the frontier while avoiding the pitfalls, Protein Sci, 19, pp. 642-657, (2010)
[54]  
Johnson J.L., Craig E.A., An essential role for the substrate-binding region of Hsp40s in Saccharomyces cerevisiae, J Cell Biol, 152, pp. 851-856, (2001)
[55]  
Kampinga H.H., Craig E.A., The HSP70 chaperone machinery: J proteins as drivers of functional specificity, Nat Rev Mol Cell Bio, 11, pp. 579-592, (2010)
[56]  
Karagoz G.E., Duarte A.M., Ippel H., Uetrecht C., Sinnige T., van Rosmalen M., Hausmann J., Heck A.J., Boelens R., Rudiger S.G., N-terminal domain of human Hsp90 triggers binding to the cochaperone p23, Proc Natl Acad Sci U S A, 108, pp. 580-585, (2011)
[57]  
Karzai A.W., McMacken R., A bipartite signaling mechanism involved in DnaJ-mediated activation of the Escherichia coli DnaK protein, J Biol Chem, 271, pp. 11236-11246, (1996)
[58]  
Kaul S.C., Deocaris C.C., Wadhwa R., Three faces of mortalin: a housekeeper, guardian and killer, Exp Gerontol, 42, pp. 263-274, (2007)
[59]  
Kikhney A.G., Svergun D.I., A practical guide to small angle X-ray scattering (SAXS) of flexible and intrinsically disordered proteins, FEBS Lett, 589, pp. 2570-2577, (2015)
[60]  
Koch M.H.J., Vachette P., Svergun D.I., Small-angle scattering: a view on the properties, structures and structural changes of biological macromolecules in solution, Q Rev Biophys, 36, pp. 147-227, (2003)
12345678910