Advanced

Differences in Backbone Dynamics of Two Homologous Bacterial Albumin-binding Modules: Implications for Binding Specificity and Bacterial Adaptation.

Johansson, Maria U; Nilsson, Hanna LU ; Evenäs, Johan; Forsén, Sture LU ; Drakenberg, Torbjörn LU ; Björck, Lars LU and Wikström, Mats (2002) In Journal of Molecular Biology 316(5). p.1083-1099
Abstract
Proteins G and PAB are bacterial albumin-binding proteins expressed at the surface of group C and G streptococci and Peptostreptococcus magnus, respectively. Repeated albumin-binding domains, known as GA modules, are found in both proteins. The third GA module of protein G from the group G streptococcal strain G148 (G148-GA3) and the second GA module of protein PAB from P.magnus strain ALB8 (ALB8-GA) exhibit 59% sequence identity and both fold to form three-helix bundle structures that are very stable against thermal denaturation. ALB8-GA binds human serum albumin with higher affinity than G148-GA3, but G148-GA3 shows substantially broader albumin-binding specificity than ALB8-GA. The (15)N nuclear magnetic resonance spin relaxation... (More)
Proteins G and PAB are bacterial albumin-binding proteins expressed at the surface of group C and G streptococci and Peptostreptococcus magnus, respectively. Repeated albumin-binding domains, known as GA modules, are found in both proteins. The third GA module of protein G from the group G streptococcal strain G148 (G148-GA3) and the second GA module of protein PAB from P.magnus strain ALB8 (ALB8-GA) exhibit 59% sequence identity and both fold to form three-helix bundle structures that are very stable against thermal denaturation. ALB8-GA binds human serum albumin with higher affinity than G148-GA3, but G148-GA3 shows substantially broader albumin-binding specificity than ALB8-GA. The (15)N nuclear magnetic resonance spin relaxation measurements reported here, show that the two GA modules exhibit mobility on the picosecond-nanosecond time scale in directly corresponding regions (loops and termini). Most residues in G148-GA3 were seen to be involved in conformational exchange processes on the microsecond-millisecond time scale, whereas for ALB8-GA such motions were only identified for the beginning of helix 2 and its preceding loop. Furthermore, and more importantly, hydrogen-deuterium exchange and saturation transfer experiments reveal large differences between the two GA modules with respect to motions on the second-hour time scale. The high degree of similarity between the two GA modules with respect to sequence, structure and stability, and the observed differences in dynamics, binding affinity and binding specificity to different albumins, suggest a distinct correlation between dynamics, binding affinity and binding specificity. Finally, it is noteworthy in this context that the module G148-GA3, which has broad albumin-binding specificity, is expressed by group C and G streptococci known to infect all mammalian species, whereas P.magnus with the ALB8-GA module has been isolated only from humans. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Rotation, Tertiary, Protein Structure, Secondary, Protein Binding, Peptostreptococcus/*chemistry/classification, Molecular Sequence Data, Molecular, Models, Magnetic Resonance Spectroscopy, Kinetics, Hydrogen/metabolism, Human, Diffusion, Comparative Study, Carrier Proteins/*chemistry/*metabolism, Binding Sites, Bacterial Proteins/*chemistry/*metabolism, Anisotropy, Amino Acid Sequence, Adaptation, Physiological, Sequence Alignment, Sequence Homology, Serum Albumin/*metabolism, Streptococcus/*chemistry/classification, Substrate Specificity, Support, Non-U.S. Gov't, Thermodynamics
in
Journal of Molecular Biology
volume
316
issue
5
pages
1083 - 1099
publisher
Elsevier
external identifiers
  • pmid:11884146
  • wos:000174503600008
  • scopus:0036304582
ISSN
1089-8638
DOI
10.1006/jmbi.2002.5398
language
English
LU publication?
yes
id
e090c84e-5c51-4b72-837b-df47d8cbe470 (old id 106156)
date added to LUP
2007-06-29 11:35:31
date last changed
2017-02-26 04:09:49
@article{e090c84e-5c51-4b72-837b-df47d8cbe470,
  abstract     = {Proteins G and PAB are bacterial albumin-binding proteins expressed at the surface of group C and G streptococci and Peptostreptococcus magnus, respectively. Repeated albumin-binding domains, known as GA modules, are found in both proteins. The third GA module of protein G from the group G streptococcal strain G148 (G148-GA3) and the second GA module of protein PAB from P.magnus strain ALB8 (ALB8-GA) exhibit 59% sequence identity and both fold to form three-helix bundle structures that are very stable against thermal denaturation. ALB8-GA binds human serum albumin with higher affinity than G148-GA3, but G148-GA3 shows substantially broader albumin-binding specificity than ALB8-GA. The (15)N nuclear magnetic resonance spin relaxation measurements reported here, show that the two GA modules exhibit mobility on the picosecond-nanosecond time scale in directly corresponding regions (loops and termini). Most residues in G148-GA3 were seen to be involved in conformational exchange processes on the microsecond-millisecond time scale, whereas for ALB8-GA such motions were only identified for the beginning of helix 2 and its preceding loop. Furthermore, and more importantly, hydrogen-deuterium exchange and saturation transfer experiments reveal large differences between the two GA modules with respect to motions on the second-hour time scale. The high degree of similarity between the two GA modules with respect to sequence, structure and stability, and the observed differences in dynamics, binding affinity and binding specificity to different albumins, suggest a distinct correlation between dynamics, binding affinity and binding specificity. Finally, it is noteworthy in this context that the module G148-GA3, which has broad albumin-binding specificity, is expressed by group C and G streptococci known to infect all mammalian species, whereas P.magnus with the ALB8-GA module has been isolated only from humans.},
  author       = {Johansson, Maria U and Nilsson, Hanna and Evenäs, Johan and Forsén, Sture and Drakenberg, Torbjörn and Björck, Lars and Wikström, Mats},
  issn         = {1089-8638},
  keyword      = {Rotation,Tertiary,Protein Structure,Secondary,Protein Binding,Peptostreptococcus/*chemistry/classification,Molecular Sequence Data,Molecular,Models,Magnetic Resonance Spectroscopy,Kinetics,Hydrogen/metabolism,Human,Diffusion,Comparative Study,Carrier Proteins/*chemistry/*metabolism,Binding Sites,Bacterial Proteins/*chemistry/*metabolism,Anisotropy,Amino Acid Sequence,Adaptation,Physiological,Sequence Alignment,Sequence Homology,Serum Albumin/*metabolism,Streptococcus/*chemistry/classification,Substrate Specificity,Support,Non-U.S. Gov't,Thermodynamics},
  language     = {eng},
  number       = {5},
  pages        = {1083--1099},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {Differences in Backbone Dynamics of Two Homologous Bacterial Albumin-binding Modules: Implications for Binding Specificity and Bacterial Adaptation.},
  url          = {http://dx.doi.org/10.1006/jmbi.2002.5398},
  volume       = {316},
  year         = {2002},
}