This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Neuroglobin (Ngb) (Fig. 1) predominantly expressed in brain of humans and other vertebrate is a recently identified member of the globin superfamily. Despite a low amino acid sequence identity of about 25% and below the protein displays all the key determinants of canonical 3 over 3 alpha-helical globin fold. Phyllogenetic analysis revealed that Ngb forms a class distinct from the Myoglobin and Hemoglobin of vertebrates establishing its ancient origin. Crystal structure of murine ferric Ngb at 1.5 Angstrom resolution suggests significant heterogeneity of heme orientations (Fig. 2). The heme is observed to be inserted into the protein in two different orientations with an occupancy ratio of 70:30 (1 2). Spectroscopic studies of structural dynamics indicate that fluctuations between different conformations take place on longer time scales when compared to myoglobin. Flash photolysis experiments suggest that CO recombination process occurs on microsecond time scale (3). Moreover the structure of carbonmonoxy neuroglobin reveals substantial conformational changes upon binding of CO to the ferrous heme iron involving a sliding motion of the heme (45) also evident from the difference scattering curve calculated using Crysol (Fig. 3). Time-resolved optical spectroscopy has been used to study structural dynamics but the detailed structural fluctuations cannot be readily probed. In contrast time-resolved X-ray scattering techniques are sensitive to the structural fluctuations. For instance time-resolved small-angle X-ray scattering (TR-SAXS) is sensitive to global structural changes such as size and shape of a protein in solution while time-resolved wide-angle X-ray scattering (TR-WAXS) provides rich information about tertiary and quaternary structural changes of a protein with global sensitivity. Here we propose the time-resolved experiments on the two proteins murine neuroglobin and human myoglobin using TR-SAXS and TR-WAXS techniques to investigate the mechanism of photochemical reaction leading to the photocycle (Fig.4).

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR007707-19
Application #
8363677
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (40))
Project Start
2011-08-01
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
19
Fiscal Year
2011
Total Cost
$48,646
Indirect Cost
Name
University of Chicago
Department
Miscellaneous
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Reddy, Vijay S; Nemerow, Glen R (2014) Reply to Campos: Revised structures of adenovirus cement proteins represent a consensus model for understanding virus assembly and disassembly. Proc Natl Acad Sci U S A 111:E4544-5

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