Structural improvement of unliganded simian immunodeficiency virus gp120 core by normal-mode-based X-ray crystallographic refinement
- Graduate Program of Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, One Baylor Plaza, BCM-125, Houston, TX 77030 (United States)
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, BCM-125, Houston, TX 77030 (United States)
- Department of Bioengineering, Rice University, Houston, TX 77005 (United States)
The structural model of the unliganded and fully glycosylated simian immunodeficiency virus gp120 core determined to 4.0 Å resolution was substantially improved using a recently developed normal-mode-based anisotropic B-factor refinement method. The envelope protein gp120/gp41 of simian and human immunodeficiency viruses plays a critical role in viral entry into host cells. However, the extraordinarily high structural flexibility and heavy glycosylation of the protein have presented enormous difficulties in the pursuit of high-resolution structural investigation of some of its conformational states. An unliganded and fully glycosylated gp120 core structure was recently determined to 4.0 Å resolution. The rather low data-to-parameter ratio limited refinement efforts in the original structure determination. In this work, refinement of this gp120 core structure was carried out using a normal-mode-based refinement method that has been shown in previous studies to be effective in improving models of a supramolecular complex at 3.42 Å resolution and of a membrane protein at 3.2 Å resolution. By using only the first four nonzero lowest-frequency normal modes to construct the anisotropic thermal parameters, combined with manual adjustments and standard positional refinement using REFMAC5, the structural model of the gp120 core was significantly improved in many aspects, including substantial decreases in R factors, better fitting of several flexible regions in electron-density maps, the addition of five new sugar rings at four glycan chains and an excellent correlation of the B-factor distribution with known structural flexibility. These results further underscore the effectiveness of this normal-mode-based method in improving models of protein and nonprotein components in low-resolution X-ray structures.
- OSTI ID:
- 22351171
- Journal Information:
- Acta Crystallographica. Section D: Biological Crystallography, Vol. 65, Issue Pt 4; Other Information: PMCID: PMC2659883; PMID: 19307715; PUBLISHER-ID: gx5139; OAI: oai:pubmedcentral.nih.gov:2659883; Copyright (c) International Union of Crystallography 2009; Country of input: International Atomic Energy Agency (IAEA); ISSN 0907-4449
- Country of Publication:
- Denmark
- Language:
- English
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