PDBsum entry 5d6h

Chaperone/protein transport

PDB id: 5d6h

Contents

Protein chains

223 a.a.

98 a.a.

Waters ×158

References listed in PDB file

Key reference

• Title: Structural insight into archaic and alternative chaperone-Usher pathways reveals a novel mechanism of pilus biogenesis.
• Authors: N.Pakharukova, J.A.Garnett, M.Tuittila, S.Paavilainen, M.Diallo, Y.Xu, S.J.Matthews, A.V.Zavialov.
• Ref.: Plos Pathog, 2015, 11, e1005269. [DOI no: 10.1371/journal.ppat.1005269]
• PubMed id: 26587649

Abstract

Gram-negative pathogens express fibrous adhesive organelles that mediate targeting to sites of infection. The major class of these organelles is assembled via the classical, alternative and archaic chaperone-usher pathways. Although non-classical systems share a wider phylogenetic distribution and are associated with a range of diseases, little is known about their assembly mechanisms. Here we report atomic-resolution insight into the structure and biogenesis of Acinetobacter baumannii Csu and Escherichia coli ECP biofilm-mediating pili. We show that the two non-classical systems are structurally related, but their assembly mechanism is strikingly different from the classical assembly pathway. Non-classical chaperones, unlike their classical counterparts, maintain subunits in a substantially disordered conformational state, akin to a molten globule. This is achieved by a unique binding mechanism involving the register-shifted donor strand complementation and a different subunit carboxylate anchor. The subunit lacks the classical pre-folded initiation site for donor strand exchange, suggesting that recognition of its exposed hydrophobic core starts the assembly process and provides fresh inspiration for the design of inhibitors targeting chaperone-usher systems.

Secondary reference #1

• Title: Crystallization and preliminary X-Ray diffraction analysis of the csu pili csuc-Csua/b chaperone-Major subunit pre-Assembly complex from acinetobacter baumannii.
• Authors: N.Pakharukova, M.Tuittila, S.Paavilainen, A.Zavialov.
• Ref.: Acta Crystallogr F Struct Biol Commun, 2015, 71, 770-774. [DOI no: 10.1107/S2053230X15007955]
• PubMed id: 26057810