Structural conservation of the PIN domain active site across all domains of life

TY - JOUR

T1 - Structural conservation of the PIN domain active site across all domains of life

AU - Senissar, M

AU - Manav, M C

AU - Brodersen, D E

N1 - © 2017 The Protein Society.

PY - 2017

Y1 - 2017

N2 - The PIN (PilT N-terminus) domain is a compact RNA-binding protein domain present in all domains of life. This 120-residue domain consists of a central and parallel β sheet surrounded by α helices, which together organize 4–5 acidic residues in an active site that binds one or more divalent metal ions and in many cases has endoribonuclease activity. In bacteria and archaea, the PIN domain is primarily associated with toxin–antitoxin loci, consisting of a toxin (the PIN domain nuclease) and an antitoxin that inhibits the function of the toxin under normal growth conditions. During nutritional or antibiotic stress, the antitoxin is proteolytically degraded causing activation of the PIN domain toxin leading to a dramatic reprogramming of cellular metabolism to cope with the new situation. In eukaryotes, PIN domains are commonly found as parts of larger proteins and are involved in a range of processes involving RNA cleavage, including ribosomal RNA biogenesis and nonsense-mediated mRNA decay. In this review, we provide a comprehensive overview of the structural characteristics of the PIN domain and compare PIN domains from all domains of life in terms of structure, active site architecture, and activity.

AB - The PIN (PilT N-terminus) domain is a compact RNA-binding protein domain present in all domains of life. This 120-residue domain consists of a central and parallel β sheet surrounded by α helices, which together organize 4–5 acidic residues in an active site that binds one or more divalent metal ions and in many cases has endoribonuclease activity. In bacteria and archaea, the PIN domain is primarily associated with toxin–antitoxin loci, consisting of a toxin (the PIN domain nuclease) and an antitoxin that inhibits the function of the toxin under normal growth conditions. During nutritional or antibiotic stress, the antitoxin is proteolytically degraded causing activation of the PIN domain toxin leading to a dramatic reprogramming of cellular metabolism to cope with the new situation. In eukaryotes, PIN domains are commonly found as parts of larger proteins and are involved in a range of processes involving RNA cleavage, including ribosomal RNA biogenesis and nonsense-mediated mRNA decay. In this review, we provide a comprehensive overview of the structural characteristics of the PIN domain and compare PIN domains from all domains of life in terms of structure, active site architecture, and activity.

KW - Journal Article

KW - Review

UR - http://www.scopus.com/inward/record.url?scp=85019844759&partnerID=8YFLogxK

U2 - 10.1002/pro.3193

DO - 10.1002/pro.3193

M3 - Journal article

C2 - 28508407

SN - 0961-8368

VL - 26

SP - 1474

EP - 1492

JO - Protein Science

JF - Protein Science

IS - 8

ER -