Building Protein Atomic Models from Cryo-EM Density Maps and Residue Co-Evolution.
co-evolution
cryo-EM
minimum spanning tree
model building
type 6 secretion system
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
13 09 2022
13 09 2022
Historique:
received:
29
07
2022
revised:
01
09
2022
accepted:
09
09
2022
entrez:
23
9
2022
pubmed:
24
9
2022
medline:
28
9
2022
Statut:
epublish
Résumé
Electron cryo-microscopy (cryo-EM) has emerged as a powerful method by which to obtain three-dimensional (3D) structures of macromolecular complexes at atomic or near-atomic resolution. However, de novo building of atomic models from near-atomic resolution (3-5 Å) cryo-EM density maps is a challenging task, in particular because poorly resolved side-chain densities hamper sequence assignment by automatic procedures at a lower resolution. Furthermore, segmentation of EM density maps into individual subunits remains a difficult problem when the structure of the subunits is not known, or when significant conformational rearrangement occurs between the isolated and associated form of the subunits. To tackle these issues, we have developed a graph-based method to thread most of the C-α trace of the protein backbone into the EM density map. The EM density is described as a weighted graph such that the resulting minimum spanning tree encompasses the high-density regions of the map. A pruning algorithm cleans the tree and finds the most probable positions of the C-α atoms, by using side-chain density when available, as a collection of C-α trace fragments. By complementing experimental EM maps with contact predictions from sequence co-evolutionary information, we demonstrate that this approach can correctly segment EM maps into individual subunits and assign amino acid sequences to backbone traces to generate atomic models.
Identifiants
pubmed: 36139128
pii: biom12091290
doi: 10.3390/biom12091290
pmc: PMC9496541
pii:
doi:
Substances chimiques
Macromolecular Substances
0
Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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