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Exploring the RNA‐bound and RNA‐free human Argonaute‐2 by molecular dynamics simulation method
Author(s) -
Kong Ren,
Xu Lei,
Piao Lianhua,
Zhang Dawei,
Hou TingJun,
Chang Shan
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12997
Subject(s) - piwi interacting rna , argonaute , rna , microbiology and biotechnology , rna silencing , chemistry , biology , biophysics , small interfering rna , computational biology , gene , biochemistry , rna interference
Argonaute 2 (Ago2) protein is the major vehicle of micro RNA s (mi RNA s)‐guided gene repression and silencing processes. Although the crystal structure of human Ago2 ( hA go2) has recently been disclosed, the information of dynamically structural character of protein– RNA recognition is still lacking. Molecular dynamics simulations were used to systematically explore hA go2 in the presence and absence of RNA duplex. Stable direct and water‐mediated hydrogen bonds were observed between guide RNA backbone atoms and hA go2, especially for nucleotides 2–7. In addition, water‐mediated hydrogen bonds are indicated to be critical in the specific recognition between hA go2 and the conserved adenine in position 1 of target RNA . The core domains (N, PAZ , MID , and PIWI ) possess rigid body movements during the simulations. The motions of N‐ PAZ and PIWI ‐ MID are negatively correlated with or without RNA binding and PAZ domain is identified as the most mobile domain in both systems. The reorientation of PAZ domain not only influences the binding of helix‐7 and RNA duplex, the initial pairing process, but also the shape of N‐ PAZ cleft, where the supplemental base pairing occurs. It is speculated that PAZ domain could be a key regulator in hA go2‐mediated mi RNA ‐induced gene regulation.