Application of the use of high‐throughput technologies to the determination of protein structures of bacterial and viral pathogens

M J Fogg; M Bahar; P Alzari; I Bertini; J‐M Betton; W P Burmeister; C Cambillau; M Coll; B Canard; M Carrondo; S Daenke; O Dym; A Geerlof; M‐P Egloff; A Haouz; F J Enguita; T A Jones; Qingjun Ma; S N Manicka; RJ Owens; M Migliardi; P Nordlund; Y Peleg; G Schneider; R Schnell; D I Stuart; T Unge; N Tarbouriech; A J Wilkinson; M Wilmanns; K S Wilson; O Zimhony; J M Grimes

doi:10.1107/S0907444906030915

. 2006 Oct 4;62(10):1196–1207. doi: 10.1107/S0907444906030915

Application of the use of high‐throughput technologies to the determination of protein structures of bacterial and viral pathogens

M J Fogg ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, M Bahar ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, P Alzari ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, I Bertini ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, J‐M Betton ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, W P Burmeister ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, C Cambillau ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, M Coll ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, B Canard ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, M Carrondo ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, S Daenke ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, O Dym ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, A Geerlof ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, M‐P Egloff ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, A Haouz ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, F J Enguita ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, T A Jones ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, Qingjun Ma ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, S N Manicka ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, RJ Owens ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, M Migliardi ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, P Nordlund ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, Y Peleg ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, G Schneider ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, R Schnell ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, D I Stuart ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, T Unge ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, N Tarbouriech ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, A J Wilkinson ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, M Wilmanns ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, K S Wilson ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, O Zimhony ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³, J M Grimes ^1,^2,^3,^4,^5,^6,^7,^8,^9,^10,^11,^12,¹³

PMCID: PMC7161641 PMID: 17001096

Abstract

The Structural Proteomics In Europe (SPINE) programme is aimed at the development and implementation of high‐throughput technologies for the efficient structure determination of proteins of biomedical importance, such as those of bacterial and viral pathogens linked to human health. Despite the challenging nature of some of these targets, 175 novel pathogen protein structures (∼220 including complexes) have been determined to date. Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens.

Keywords: automation, miniaturization, cloning, expression, viruses, bacteria.

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Application of the use of high‐throughput technologies to the determination of protein structures of bacterial and viral pathogens

M J Fogg

M Bahar

P Alzari

I Bertini

J‐M Betton

W P Burmeister

C Cambillau

M Coll

B Canard

M Carrondo

S Daenke

O Dym

A Geerlof

M‐P Egloff

A Haouz

F J Enguita

T A Jones

Qingjun Ma

S N Manicka

RJ Owens

M Migliardi

P Nordlund

Y Peleg

G Schneider

R Schnell

D I Stuart

T Unge

N Tarbouriech

A J Wilkinson

M Wilmanns

K S Wilson

O Zimhony

J M Grimes

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