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Distinct ways of G:U recognition by conserved tRNA binding motifs.

Abstract：

:Throughout three domains of life, alanyl-tRNA synthetases (AlaRSs) recognize a G3:U70 base pair in the acceptor stem of tRNAAla as the major identity determinant of tRNAAla The crystal structure of the archaeon Archaeoglobus fulgidus AlaRS in complex with tRNAAla provided the basis for G3:U70 recognition with residues (Asp and Asn) that are conserved in the three domains [Naganuma M, et al. (2014) Nature 510:507-511]. The recognition mode is unprecedented, with specific accommodation of the dyad asymmetry of the G:U wobble pair and exclusion of the dyad symmetry of a Watson-Crick pair. With this conserved mode, specificity is based more on "fit" than on direct recognition of specific atomic groups. Here, we show that, in contrast to the archaeal complex, the Escherichia coli enzyme uses direct positive (energetically favorable) minor groove recognition of the unpaired 2-amino of G3 by Asp and repulsion of a competing base pair by Asn. Strikingly, mutations that disrupted positive recognition by the E. coli enzyme had little or no effect on G:U recognition by the human enzyme. Alternatively, Homo sapiens AlaRS selects G:U without positive recognition and uses Asp instead to repel a competitor. Thus, the widely conserved Asp-plus-Asn architecture of AlaRSs can select G:U in a straightforward (bacteria) or two different unconventional (eukarya/archaea) ways. The adoption of different modes for recognition of a widely conserved G:U pair in alanine tRNAs suggests an early and insistent role for G:U in the development of the genetic code.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Chong YE,Guo M,Yang XL,Kuhle B,Naganuma M,Sekine SI,Yokoyama S,Schimmel P

doi

10.1073/pnas.1807109115

subject

Has Abstract

pub_date

2018-07-17 00:00:00

pages

7527-7532

issue

29

eissn

0027-8424

issn

1091-6490

pii

1807109115

journal_volume

115

pub_type

杂志文章

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