Modulation of hemoglobin dynamics by an allosteric effector

Lal, Jyotsana; Maccarini, Marco; Fouquet, Peter; Ho, Nancy T.; Ho, Chien; Makowski, Lee

doi:10.1002/pro.3099

Modulation of hemoglobin dynamics by an allosteric effector

Journal Article · Wed Dec 14 23:00:00 EST 2016 · Protein Science

DOI:https://doi.org/10.1002/pro.3099· OSTI ID:1365389

Lal, Jyotsana ^[1]; Maccarini, Marco ^[2]; Fouquet, Peter ^[3]; Ho, Nancy T. ^[4]; Ho, Chien ^[4]; Makowski, Lee ^[5]

Argonne National Lab. (ANL), Argonne, IL (United States); Boston Univ., Boston, MA (United States)
Institut Laue-Langevin (France); Univ. Grenoble Alpes, Grenoble (France)
Institut Laue-Langevin (France)
Carnegie Mellon Univ., Pittsburgh, PA (United States)
Argonne National Lab. (ANL), Argonne, IL (United States); Northeastern Univ., Boston, MA (United States)

Hemoglobin (Hb) is an extensively studied paradigm of proteins that alter their function in response to allosteric effectors. Models of its action have been used as prototypes for structure-function relationships in many proteins, and models for the molecular basis of its function have been deeply studied and extensively argued. Recent reports suggest that dynamics may play an important role in its function. Relatively little is known about the slow, correlated motions of hemoglobin subunits in various structural states because experimental and computational strategies for their characterization are challenging. Allosteric effectors such as inositol hexaphosphate (IHP) bind to both deoxy-Hb and HbCO, albeit at different sites, leading to a lowered oxygen affinity. The manner in which these effectors impact oxygen binding is unclear and may involve changes in structure, dynamics or both. Here we use neutron spin echo (NSE) measurements accompanied by wideangle x-ray scattering (WAXS) to show that binding of IHP to HbCO results in an increase in the rate of coordinated motions of Hb subunits relative to one another with little if any change in large scale structure. This increase of large-scale dynamics seems to be coupled with a decrease in the average magnitude of higher frequency modes of individual residues. Furthermore, these observations indicate that enhanced dynamic motions contribute to the functional changes induced by IHP and suggest that they may be responsible for the lowered oxygen affinity triggered by these effectors.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22), Scientific User Facilities Division

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1365389

Journal Information:: Protein Science, Journal Name: Protein Science Journal Issue: 3 Vol. 26; ISSN 0961-8368

Publisher:: The Protein SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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allosteric
hemoglobin
neutron spin echo
protein dynamics
x-ray solution scattering

Modulation of hemoglobin dynamics by an allosteric effector

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