Crystallography and protein-protein interactions: Biological interfaces and crystal contacts

Kobe, Bostjan, Guncar, Gregor, Buchholz, Rebecca, Huber, Thomas, Maco, Bohumil, Cowieson, Nathan, Martin, Jennifer L., Marfori, Mary and Forwood, Jade K. (2008) Crystallography and protein-protein interactions: Biological interfaces and crystal contacts. Biochemical Society Transactions, 36 6: 1438-1441. doi:10.1042/BST0361438


Author Kobe, Bostjan
Guncar, Gregor
Buchholz, Rebecca
Huber, Thomas
Maco, Bohumil
Cowieson, Nathan
Martin, Jennifer L.
Marfori, Mary
Forwood, Jade K.
Title Crystallography and protein-protein interactions: Biological interfaces and crystal contacts
Journal name Biochemical Society Transactions   Check publisher's open access policy
ISSN 0300-5127
1470-8752
Publication date 2008-12-01
Sub-type Article (original research)
DOI 10.1042/BST0361438
Volume 36
Issue 6
Start page 1438
End page 1441
Total pages 4
Editor D. Richardson
Place of publication Colchester, U.K.
Publisher Portland Press
Collection year 2009
Language eng
Subject C1
060112 Structural Biology (incl. Macromolecular Modelling)
970106 Expanding Knowledge in the Biological Sciences
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
Abstract 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. © The Authors Journal compilation © 2008 Biochemical Society
Keyword Acyl-CoA thioesterase 7 (Acot7)
Platelet glycoprotein lb alpha
Protein-protein interaction
Structural biology
Thrombin
X-ray crystallography
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Thu, 26 Feb 2009, 01:07:20 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences