Journal Article

FZJ-2017-01570

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Unifying view of mechanical and functional hotspots across class A GPCRs

Ponzoni, L. (Corresponding author) ; Rossetti, G. (Corresponding author)FZJ* ; Maggi, L. ; Giorgetti, A.FZJ* ; Carloni, P.FZJ* ; Micheletti, C.

2017
Public Library of Science San Francisco, Calif.

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/13886  doi:10.1371/journal.pcbi.1005381

Abstract: G protein-coupled receptors (GPCRs) are the largest superfamily of signaling proteins. Their activation process is accompanied by conformational changes that have not yet been fully uncovered. Here, we carry out a novel comparative analysis of internal structural fluctuations across a variety of receptors from class A GPCRs, which currently has the richest structural coverage. We infer the local mechanical couplings underpinning the receptors’ functional dynamics and finally identify those amino acids whose virtual deletion causes a significant softening of the mechanical network. The relevance of these amino acids is demonstrated by their overlap with those known to be crucial for GPCR function, based on static structural criteria. The differences with the latter set allow us to identify those sites whose functional role is more clearly detected by considering dynamical and mechanical properties. Of these sites with a genuine mechanical/dynamical character, the top ranking is amino acid 7x52, a previously unexplored, and experimentally verifiable key site for GPCR conformational response to ligand binding.

---

Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Jara-Institut Quantum Information (INM-11)
3. Computational Biomedicine (INM-9)
4. Jülich Supercomputing Center (JSC)
5. JARA - HPC (JARA-HPC)

Research Program(s):

1. 574 - Theory, modelling and simulation (POF3-574) (POF3-574)
2. 511 - Computational Science and Mathematical Methods (POF3-511) (POF3-511)
3. Towards the design of allosteric ligands binding to the human muscarinic receptor M2 (jias59_20161101) (jias59_20161101)

Appears in the scientific report 2017

---

Database coverage:
; ; ; ; BIOSIS Previews ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---