Conformational Dynamics from Ambiguous Zinc Coordination in the RanBP2-Type Zinc Finger of RBM5.
J Mol Biol
; 432(14): 4127-4138, 2020 06 26.
Article
de En
| MEDLINE
| ID: mdl-32450081
ABSTRACT
The multi-domain RNA binding protein RBM5 is a molecular signature of metastasis. RBM5 regulates alternative splicing of apoptotic genes including the cell death receptor Fas and the initiator Caspase-2. The RBM5 RanBP2-type zinc finger (Zf1) is known to specifically recognize single-stranded RNAs with high affinity. Here, we study the structure and conformational dynamics of the Zf1 zinc finger of human RBM5 using NMR. We show that the presence of a non-canonical cysteine in Zf1 kinetically destabilizes the protein. Metal-exchange kinetics show that mutation of the cysteine establishes high-affinity coordination of the zinc. Our data indicate that selection of such a structurally destabilizing mutation during the course of evolution could present an opportunity for functional adaptation of the protein.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Doigts de zinc
/
Protéines de liaison à l'ARN
/
Chaperons moléculaires
/
Protéines du cycle cellulaire
/
Complexe protéique du pore nucléaire
/
Protéines suppresseurs de tumeurs
/
Protéines de liaison à l'ADN
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
J Mol Biol
Année:
2020
Type de document:
Article
Pays d'affiliation:
Allemagne