The Convergence of the Hedgehog/Intein Fold in Different Protein Splicing Mechanisms.

Abstract:

:Protein splicing catalyzed by inteins utilizes many different combinations of amino-acid types at active sites. Inteins have been classified into three classes based on their characteristic sequences. We investigated the structural basis of the protein splicing mechanism of class 3 inteins by determining crystal structures of variants of a class 3 intein from Mycobacterium chimaera and molecular dynamics simulations, which suggested that the class 3 intein utilizes a different splicing mechanism from that of class 1 and 2 inteins. The class 3 intein uses a bond cleavage strategy reminiscent of proteases but share the same Hedgehog/INTein (HINT) fold of other intein classes. Engineering of class 3 inteins from a class 1 intein indicated that a class 3 intein would unlikely evolve directly from a class 1 or 2 intein. The HINT fold appears as structural and functional solution for trans-peptidyl and trans-esterification reactions commonly exploited by diverse mechanisms using different combinations of amino-acid types for the active-site residues.

journal_name

Int J Mol Sci

authors

Beyer HM,Virtanen SI,Aranko AS,Mikula KM,Lountos GT,Wlodawer A,Ollila OHS,Iwaï H

doi

10.3390/ijms21218367

subject

Has Abstract

pub_date

2020-11-07 00:00:00

issue

21

issn

1422-0067

pii

ijms21218367

journal_volume

21

pub_type

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