Flexible Linker Modulates Glycosaminoglycan Affinity of Decorin Binding Protein A

Ashli Morgan, Krishna Mohan Sepuru, Wei Feng, Krishna Rajarathnam, Xu Wang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Decorin binding protein A (DBPA) is a glycosaminoglycan (GAG)-binding adhesin found on the surface of the bacterium Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme disease. DBPA facilitates bacterial adherence to extracellular matrices of human tissues and is crucial during the early stage of the infection process. Interestingly, DBPA from different strains (B31, N40, and PBr) show significant differences in GAG affinities, but the structural basis for the differences is not clear. In this study, we show that GAG affinity of N40 DBPA is modulated in part by flexible segments that control access to the GAG binding site, such that shortening of the linker leads to higher GAG affinity when analyzed using ELISA, gel mobility shift assay, solution NMR, and isothermal titration calorimetry. Our observation that GAG affinity differences among different B. burgdorferi strains can be attributed to a flexible linker domain regulating access to the GAG-binding domain is novel. It also provides a rare example of how neutral amino acids and dynamic segments in GAG binding proteins can have a large influence on GAG affinity and provides insights into why the number of basic amino acids in the GAG-binding site may not be the only factor determining GAG affinity of proteins.

Original languageEnglish (US)
Pages (from-to)5113-5119
Number of pages7
JournalBiochemistry
Volume54
Issue number32
DOIs
StatePublished - Jul 30 2015

Fingerprint

Decorin
Staphylococcal Protein A
Glycosaminoglycans
Carrier Proteins
Borrelia burgdorferi
Binding Sites
Neutral Amino Acids
Basic Amino Acids
Calorimetry
Lyme Disease
Electrophoretic Mobility Shift Assay
Titration
Access control
Extracellular Matrix
Assays
Bacteria

ASJC Scopus subject areas

  • Biochemistry

Cite this

Flexible Linker Modulates Glycosaminoglycan Affinity of Decorin Binding Protein A. / Morgan, Ashli; Sepuru, Krishna Mohan; Feng, Wei; Rajarathnam, Krishna; Wang, Xu.

In: Biochemistry, Vol. 54, No. 32, 30.07.2015, p. 5113-5119.

Research output: Contribution to journalArticle

Morgan, Ashli ; Sepuru, Krishna Mohan ; Feng, Wei ; Rajarathnam, Krishna ; Wang, Xu. / Flexible Linker Modulates Glycosaminoglycan Affinity of Decorin Binding Protein A. In: Biochemistry. 2015 ; Vol. 54, No. 32. pp. 5113-5119.
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