English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Collective dynamics underlying allosteric transitions in hemoglobin.

Vesper, M. D., & de Groot, B. L. (2013). Collective dynamics underlying allosteric transitions in hemoglobin. PLoS Computational Biology, 9(9): e1003232. doi:10.1371/journal.pcbi.1003232.

Item is

Files

show Files
hide Files
:
1850714.pdf (Publisher version), 2MB
Name:
1850714.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Creators

show
hide
 Creators:
Vesper, M. D.1, Author           
de Groot, B. L.1, Author           
Affiliations:
1Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society, ou_578573              

Content

show
hide
Free keywords: -
 Abstract: Hemoglobin is the prototypic allosteric protein. Still, its molecular allosteric mechanism is not fully understood. To elucidate the mechanism of cooperativity on an atomistic level, we developed a novel computational technique to analyse the coupling of tertiary and quaternary motions. From Molecular Dynamics simulations showing spontaneous quaternary transitions, we separated the transition trajectories into two orthogonal sets of motions: one consisting of intra-chain motions only (referred to as tertiary-only) and one consisting of global inter-chain motions only (referred to as quaternaryonly). The two underlying subspaces are orthogonal by construction and their direct sum is the space of full motions. Using Functional Mode Analysis, we were able to identify a collective coordinate within the tertiary-only subspace that is correlated to the most dominant motion within the quaternary-only motions, hence providing direct insight into the allosteric coupling mechanism between tertiary and quaternary conformation changes. This coupling-motion is substantially different from tertiary structure changes between the crystallographic structures of the T-and R-state. We found that hemoglobin's allosteric mechanism of communication between subunits is equally based on hydrogen bonds and steric interactions. In addition, we were able to affect the T- to -R transition rates by choosing different histidine protonation states, thereby providing a possible atomistic explanation for the Bohr effect.

Details

show
hide
Language(s): eng - English
 Dates: 2013-09-19
 Publication Status: Published online
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1371/journal.pcbi.1003232
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: PLoS Computational Biology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 9 (9) Sequence Number: e1003232 Start / End Page: - Identifier: -