Crystallography is commonly used for studying the structures of protein–protein complexes. However, a crystal structure does not define a unique protein–protein interface, and distinguishing a ‘biological interface’ from ‘crystal contacts’ is often not straightforward. A number of computational approaches exist for distinguishing them, but their error rate is high, emphasizing the need to obtain further data on the biological interface using complementary structural and functional approaches. In addition to reviewing the computational and experimental approaches for addressing this problem, we highlight two relevant examples. The first example from our laboratory involves the structure of acyl-CoA thioesterase 7, where each domain of this two-domain protein was crystallized separately, but both yielded a non-functional assembly. The structure of the full-length protein was uncovered using a combination of complementary approaches including chemical cross-linking, analytical ultracentrifugation and mutagenesis. The second example involves the platelet glycoprotein Ibα–thrombin complex. Two groups reported the crystal structures of this complex, but all the interacting interfaces differed between the two structures. Our computational analysis did not fully resolve the reasons for the discrepancies, but provided interesting insights into the system. This review highlights the need to complement crystallographic studies with complementary experimental and computational approaches.
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December 2008
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Conference Article|
November 19 2008
Crystallography and protein–protein interactions: biological interfaces and crystal contacts
Bostjan Kobe;
Bostjan Kobe
1
*School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
†Institute for Molecular Bioscience and Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane, QLD 4072, Australia
1To whom correspondence should be addressed (email b.kobe@uq.edu.au).
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Gregor Guncar;
Gregor Guncar
*School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
‡Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Ljubljana, Slovenia
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Rebecca Buchholz;
Rebecca Buchholz
*School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
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Thomas Huber;
Thomas Huber
*School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
§Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
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Bohumil Maco;
Bohumil Maco
*School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
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Nathan Cowieson;
Nathan Cowieson
†Institute for Molecular Bioscience and Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane, QLD 4072, Australia
∥Monash Centre for Synchrotron Science, Monash University, Clayton, VIC 3800, Australia
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Jennifer L. Martin;
Jennifer L. Martin
†Institute for Molecular Bioscience and Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane, QLD 4072, Australia
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Mary Marfori;
Mary Marfori
*School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
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Jade K. Forwood
Jade K. Forwood
*School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
¶School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia
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Publisher: Portland Press Ltd
Received:
August 11 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (6): 1438–1441.
Article history
Received:
August 11 2008
Citation
Bostjan Kobe, Gregor Guncar, Rebecca Buchholz, Thomas Huber, Bohumil Maco, Nathan Cowieson, Jennifer L. Martin, Mary Marfori, Jade K. Forwood; Crystallography and protein–protein interactions: biological interfaces and crystal contacts. Biochem Soc Trans 1 December 2008; 36 (6): 1438–1441. doi: https://doi.org/10.1042/BST0361438
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