NMR in structural genomics to increase structural coverage of the protein universe.
NMR in structural genomics to increase structural coverage of the protein universe.
FEBS J. 2016 May 7;
Authors: Serrano P, Dutta SK, Proudfoot A, Mohanty B, Susac L, Martin B, Geralt M, Jaroszewski L, Godzik A, Elsliger M, Wilson IA, Wüthrich K
Abstract
For more than a decade, the Joint Center for Structural Genomics (JCSG; www . jcsg . org) worked toward increased three-dimensional structure coverage of the protein universe. This coordinated quest was one of the main goals of the four high-throughput (HT) structure determination centers of the Protein Structure Initiative (PSI; www . nigms . nih . gov/Research/specificareas/PSI). To achieve the goals of the PSI, the JCSG made use of the complementarity of structure determination by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy to increase and diversify the range of targets entering the HT structure determination pipeline. The overall strategy, for both techniques, was to determine atomic resolution structures for representatives of large protein families, as defined by the Pfam database, which had no structural coverage and could make significant contributions to biological and biomedical research. Furthermore, the experimental structures could be leveraged by homology modeling to further expand the structural coverage of the protein universe and increase biological insights. Here, we describe what could be achieved by this structural genomics approach, using as an illustration the contributions from 20 NMR structure determinations out of a total of 98 JCSG NMR structures, which were selected because they are the first three-dimensional structure representations of the respective Pfam protein families. The information from this small sample is representative for the overall results from crystal and NMR structure determination in the JCSG. There are five new folds, which were classified as domains of unknown functions (DUF), three of the proteins could be functionally annotated based on three-dimensional structure similarity with previously characterized proteins, and twelve proteins showed only limited similarly with previous deposits in the protein data bank (PDB) and were classified as DUFs. This article is protected by copyright. All rights reserved.
PMID: 27154589 [PubMed - as supplied by publisher]
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