Anchored clathrate waters bind antifreeze proteins to ice

Edited by Michael Levitt, Stanford University School of Medicine, Stanford, CA, and approved March 8, 2011 (received for review January 10, 2011)
April 11, 2011
108 (18) 7363-7367
Commentary
A peek at ice binding by antifreeze proteins
Kim A. Sharp

Abstract

The mechanism by which antifreeze proteins (AFPs) irreversibly bind to ice has not yet been resolved. The ice-binding site of an AFP is relatively hydrophobic, but also contains many potential hydrogen bond donors/acceptors. The extent to which hydrogen bonding and the hydrophobic effect contribute to ice binding has been debated for over 30 years. Here we have elucidated the ice-binding mechanism through solving the first crystal structure of an Antarctic bacterial AFP. This 34-kDa domain, the largest AFP structure determined to date, folds as a Ca2+-bound parallel beta-helix with an extensive array of ice-like surface waters that are anchored via hydrogen bonds directly to the polypeptide backbone and adjacent side chains. These bound waters make an excellent three-dimensional match to both the primary prism and basal planes of ice and in effect provide an extensive X-ray crystallographic picture of the AFP∶ice interaction. This unobstructed view, free from crystal-packing artefacts, shows the contributions of both the hydrophobic effect and hydrogen bonding during AFP adsorption to ice. We term this mode of binding the “anchored clathrate” mechanism of AFP action.

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Data Availability

Data deposition: The atomic coordinates and structure factors have been deposited in the Research Collaboratory for Structural Bioinformatics Protein Data Bank, www.rcsb.org (RCSB PDB ID code 3P4G).

Acknowledgments.

We thank Jean Jakoncic and Vivian Stojanoff of the X6A beamline at Brookhaven National Laboratories for help with X-ray data acquisition and processing and Jack Gilbert for the initial discovery of M. primoryensisAFP. We also thank Dr. John Allingham for access to a Rigaku home X-ray source for initial diffraction experiments. This work was funded by the Canadian Institutes of Health Research. C.P.G. is the recipient of an Natural Sciences and Engineering Research Council of Canada three-year Postgraduate Scholarship (PGS D3). P.L.D. holds a Canada Research Chair in protein engineering.

Supporting Information

Supporting Information (PDF)
Supporting Information

References

1
JA Raymond, AL DeVries, Adsorption inhibition as a mechanism of freezing resistance in polar fishes. Proc Natl Acad Sci USA 74, 2589–2593 (1977).
2
SP Graether, et al., Beta-helix structure and ice-binding properties of a hyperactive antifreeze protein from an insect. Nature 406, 325–328 (2000).
3
T Ko, et al., The refined crystal structure of an eel pout type III antifreeze protein RD1 at 0.62-Å resolution reveals structural microheterogeneity of protein and solvation. Biophys J 84, 1228–1237 (2003).
4
YC Liou, A Tocilj, PL Davies, Z Jia, Mimicry of ice structure by surface hydroxyls and water of a beta-helix antifreeze protein. Nature 406, 322–324 (2000).
5
Y Nishimiya, et al., Crystal structure and mutational analysis of Ca2+-independent type II antifreeze protein from longsnout poacher, Brachyopsis rostratus. J Mol Biol 382, 734–746 (2008).
6
BL Pentelute, et al., X-ray structure of snow flea antifreeze protein determined by racemic crystallization of synthetic protein enantiomers. J Am Chem Soc 130, 9695–9701 (2008).
7
F Sicheri, DS Yang, Ice-binding structure and mechanism of an antifreeze protein from winter flounder. Nature 375, 427–431 (1995).
8
CH Cheng, Evolution of the diverse antifreeze proteins. Curr Opin Genet Dev 8, 715–720 (1998).
9
GL Fletcher, CL Hew, PL Davies, Antifreeze proteins of teleost fishes. Annu Rev Physiol 63, 359–390 (2001).
10
PL Davies, J Baardsnes, MJ Kuiper, VK Walker, Structure and function of antifreeze proteins. Philos Trans R Soc Lond B Biol Sci 357, 927–935 (2002).
11
AJ Scotter, et al., The basis for hyperactivity of antifreeze proteins. Cryobiology 53, 229–239 (2006).
12
AL Devries, Y Lin, Structure of a peptide antifreeze and mechanism of adsorption to ice. Biochim Biophys Acta 495, 388–392 (1977).
13
H Chao, et al., A diminished role for hydrogen bonds in antifreeze protein binding to ice. Biochemistry 36, 14652–14660 (1997).
14
J Baardsnes, et al., New ice-binding face for type I antifreeze protein. FEBS Lett 463, 87–91 (1999).
15
DR Nutt, JC Smith, Dual function of the hydration layer around an antifreeze protein revealed by atomistic molecular dynamics simulations. J Am Chem Soc 130, 13066–13073 (2008).
16
KR Gallagher, KA Sharp, Analysis of thermal hysteresis protein hydration using the random network model. Biophys Chem 105, 195–209 (2003).
17
A Jorov, BS Zhorov, DS Yang, Theoretical study of interaction of winter flounder antifreeze protein with ice. Protein Sci 13, 1524–1537 (2004).
18
N Smolin, V Daggett, Formation of ice-like water structure on the surface of an antifreeze protein. J Phys Chem B 112, 6193–6202 (2008).
19
A Wierzbicki, et al., Antifreeze proteins at the ice/water interface: Three calculated discriminating properties for orientation of type I proteins. Biophys J 93, 1442–1451 (2007).
20
C Yang, KA Sharp, The mechanism of the type III antifreeze protein action: A computational study. Biophys Chem 109, 137–148 (2004).
21
C Yang, KA Sharp, Hydrophobic tendency of polar group hydration as a major force in type I antifreeze protein recognition. Proteins 59, 266–274 (2005).
22
JA Gilbert, PL Davies, J Laybourn-Parry, A hyperactive, Ca2+-dependent antifreeze protein in an Antarctic bacterium. FEMS Microbiol Lett 245, 67–72 (2005).
23
CP Garnham, et al., A Ca2+-dependent bacterial antifreeze protein domain has a novel beta-helical ice-binding fold. Biochem J 411, 171–180 (2008).
24
JG Coote, Structural and functional relationships among the RTX toxin determinants of gram-negative bacteria. FEMS Microbiol Rev 8, 137–161 (1992).
25
FL Aachmann, et al., NMR structure of the R-module: A parallel beta-roll subunit from an Azotobacter vinelandii mannuronan C-5 epimerase. J Biol Chem 281, 7350–7356 (2006).
26
U Baumann, S Wu, KM Flaherty, DB McKay, Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: A two-domain protein with a calcium binding parallel beta roll motif. EMBO J 12, 3357–3364 (1993).
27
CP Garnham, et al., Compound ice-binding site of an antifreeze protein revealed by mutagenesis and fluorescent tagging. Biochemistry 49, 9063–9071 (2010).
28
YF Mok, et al., Structural basis for the superior activity of the large isoform of snow flea antifreeze protein. Biochemistry 49, 2593–2603 (2010).
29
CA Knight, CC Cheng, AL DeVries, Adsorption of alpha-helical antifreeze peptides on specific ice crystal surface planes. Biophys J 59, 409–418 (1991).
30
AB Siemer, KY Huang, AE McDermott, Protein–ice interaction of an antifreeze protein observed with solid-state NMR. Proc Natl Acad Sci USA 107, 17580–17585 (2010).
31
K Modig, et al., High water mobility on the ice-binding surface of a hyperactive antifreeze protein. Phys Chem Chem Phys 12, 10189–10197 (2010).
32
M Takamichi, Y Nishimiya, A Miura, S Tsuda, Effect of annealing time of an ice crystal on the activity of type III antifreeze protein. FEBS J 274, 6469–6476 (2007).
33
J Jancarik, R Pufan, C Hong, SH Kim, R Kim, Optimum solubility (OS) screening: An efficient method to optimize buffer conditions for homogeneity and crystallization of proteins. Acta Crystallogr Sect D Biol Crystallogr 60, 1670–1673 (2004).
34
Z Otwinowski, W Minor, Processing of X-ray diffraction data collected in oscillation mode., eds CW Carter, RM Sweet (Academic, New York) Vol 276, 307–326 (1997).
35
GM Sheldrick, A short history of SHELX. Acta Crystallogr Sect A Found Crystallogr 64, 112–122 (2008).
36
G Langer, SX Cohen, VS Lamzin, A Perrakis, Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7. Nat Protoc 3, 1171–1179 (2008).
37
P Emsley, K Cowtan, Coot: Model-building tools for molecular graphics. Acta Crystallogr Sect D Biol Crystallogr 60, 2126–2132 (2004).
38
GN Murshudov, AA Vagin, EJ Dodson, Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr Sect D Biol Crystallogr 53, 240–255 (1997).
39
AJ McCoy, et al., Phaser crystallographic software. J Appl Crystallogr 40, 658–674 (2007).

Information & Authors

Information

Published in

The cover image for PNAS Vol.108; No.18
Proceedings of the National Academy of Sciences
Vol. 108 | No. 18
May 3, 2011
PubMed: 21482800

Classifications

Data Availability

Data deposition: The atomic coordinates and structure factors have been deposited in the Research Collaboratory for Structural Bioinformatics Protein Data Bank, www.rcsb.org (RCSB PDB ID code 3P4G).

Submission history

Published online: April 11, 2011
Published in issue: May 3, 2011

Keywords

  1. Ca2+ binding protein
  2. repeats-in-toxin protein
  3. thermal hysteresis
  4. Antarctic bacterium
  5. organized biohydration

Acknowledgments

We thank Jean Jakoncic and Vivian Stojanoff of the X6A beamline at Brookhaven National Laboratories for help with X-ray data acquisition and processing and Jack Gilbert for the initial discovery of M. primoryensisAFP. We also thank Dr. John Allingham for access to a Rigaku home X-ray source for initial diffraction experiments. This work was funded by the Canadian Institutes of Health Research. C.P.G. is the recipient of an Natural Sciences and Engineering Research Council of Canada three-year Postgraduate Scholarship (PGS D3). P.L.D. holds a Canada Research Chair in protein engineering.

Notes

This article is a PNAS Direct Submission.
See Commentary on page 7281.

Authors

Affiliations

Christopher P. Garnham
Department of Biochemistry, Queen’s University, Kingston, ON, Canada K7L 3N6
Robert L. Campbell
Department of Biochemistry, Queen’s University, Kingston, ON, Canada K7L 3N6
Peter L. Davies1 [email protected]
Department of Biochemistry, Queen’s University, Kingston, ON, Canada K7L 3N6

Notes

1
To whom correspondence should be addressed. E-mail: [email protected].
Author contributions: C.P.G., R.L.C., and P.L.D. designed research; C.P.G. performed research; C.P.G. analyzed data; and C.P.G. wrote the paper with editorial input from P.L.D.

Competing Interests

The authors declare no conflict of interest.

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    Anchored clathrate waters bind antifreeze proteins to ice
    Proceedings of the National Academy of Sciences
    • Vol. 108
    • No. 18
    • pp. 7277-7652

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