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Title: Modulation of hemoglobin dynamics by an allosteric effector

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 ofmore » 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.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [4] ;  [5]
  1. Argonne National Lab. (ANL), Argonne, IL (United States); Boston Univ., Boston, MA (United States)
  2. Institut Laue-Langevin (France); Univ. Grenoble Alpes, Grenoble (France)
  3. Institut Laue-Langevin (France)
  4. Carnegie Mellon Univ., Pittsburgh, PA (United States)
  5. Argonne National Lab. (ANL), Argonne, IL (United States); Northeastern Univ., Boston, MA (United States)
Publication Date:
Grant/Contract Number:
AC02-06CH11357
Type:
Published Article
Journal Name:
Protein Science
Additional Journal Information:
Journal Volume: 26; Journal Issue: 3; Journal ID: ISSN 0961-8368
Publisher:
The Protein Society
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22), Scientific User Facilities Division; USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; allosteric; hemoglobin; neutron spin echo; x-ray solution scattering; protein dynamics
OSTI Identifier:
1343629
Alternate Identifier(s):
OSTI ID: 1343630; OSTI ID: 1365389