title: Progress in rational methods of cryoprotection in macromolecular crystallography.
abstract: Cryogenic cooling of macromolecular crystals is commonly used for X-ray data collection both to reduce crystal damage from radiation and to gather functional information by cryogenically trapping intermediates. However, the cooling process can damage the crystals. Limiting cooling-induced crystal damage often requires cryoprotection strategies, which can involve substantial screening of solution conditions and cooling protocols. Here, recent developments directed towards rational methods for cryoprotection are described. Crystal damage is described in the context of the temperature response of the crystal as a thermodynamic system. As such, the internal and external parts of the crystal typically have different cryoprotection requirements. A key physical parameter, the thermal contraction, of 26 different cryoprotective solutions was measured between 294 and 72 K. The range of contractions was 2-13%, with the more polar cryosolutions contracting less. The potential uses of these results in the development of cryocooling conditions, as well as recent developments in determining minimum cryosolution soaking times, are discussed.
authors.affiliation: Program in Biochemistry, Biophysics and Molecular Biology, Whitman College, Walla Walla, WA 99362, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Alcorn
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Juers
mesh_terms: D003080:Cold Temperature; D018360:Crystallography, X-Ray / Q000379:methods*; D046911:Macromolecular Substances / Q000032:analysis*; D013816:Thermodynamics
chemical_list: D046911:Macromolecular Substances
references.citation: J Biomech Eng. 1998 Apr;120(2):259-66
references.pmid: 10412388
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Dec;59(Pt 12):2169-82
references.pmid: 14646075
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Acta Crystallogr B. 1988 Feb 1;44 ( Pt 1):22-6
references.pmid: 3271102
references.citation: J Synchrotron Radiat. 2005 May;12(Pt 3):310-7
references.pmid: 15840916
references.citation: Acta Crystallogr B. 2012 Feb;68(Pt 1):91
references.pmid: 22267563
references.citation: Q Rev Biophys. 2004 May;37(2):105-19
references.pmid: 15999418
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Mar;63(Pt 3):415-9
references.pmid: 17327679
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Oct;55(Pt 10):1641-53
references.pmid: 10531512
references.citation: Methods Enzymol. 2003;368:188-216
references.pmid: 14674275
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):459-71
references.pmid: 11856832
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Apr;57(Pt 4):566-73
references.pmid: 11264586
references.citation: Curr Opin Struct Biol. 2003 Oct;13(5):545-51
references.pmid: 14568608
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Mar;60(Pt 3):412-21
references.pmid: 14993664
references.citation: Acta Crystallogr D Biol Crystallogr. 2005 Jul;61(Pt 7):982-9
references.pmid: 15983422
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):848-53
references.pmid: 9757100
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Jan;60(Pt 1):39-45
references.pmid: 14684890
references.citation: J Mol Biol. 2001 Aug 24;311(4):851-62
references.pmid: 11518535
references.citation: Structure. 1994 Dec 15;2(12):1135-40
references.pmid: 7704524
references.citation: Methods Enzymol. 1985;114:128-31
references.pmid: 4079758
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Apr;59(Pt 4):697-708
references.pmid: 12657789
references.citation: Protein Sci. 2003 Sep;12(9):1865-71
references.pmid: 12930986
references.citation: Proc Natl Acad Sci U S A. 1966 Dec;56(6):1746-50
references.pmid: 16591415
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):32-47
references.pmid: 16369092
references.citation: Acta Crystallogr D Biol Crystallogr. 1996 Sep 1;52(Pt 5):959-65
references.pmid: 15299605
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Nov;63(Pt 11):1139-53
references.pmid: 18007029
references.citation: J Appl Crystallogr. 2006 Dec 1;39(6):805-811
references.pmid: 20461232
references.citation: Biochemistry. 1987 Jan 13;26(1):254-61
references.pmid: 3828301
references.citation: Structure. 2006 Mar;14(3):393-400
references.pmid: 16531224
references.citation: J Synchrotron Radiat. 2002 Nov 1;9(Pt 6):361-7
references.pmid: 12409623
references.citation: Acta Crystallogr B Struct Crystallogr Cryst Chem. 1970 Jul 15;26(7):998-1004
references.pmid: 5536135
references.citation: J Mol Biol. 1968 Apr 28;33(2):491-7
references.pmid: 5700707