title: Exploring the sequence-structure-function relationship for the intrinsically disordered βγ-crystallin Hahellin.
abstract: βγ-Crystallins are a superfamily of proteins containing crystallin-type Greek key motifs. Some βγ-crystallin domains have been shown to bind Ca2+. Hahellin is a newly identified intrinsically disordered βγ-crystallin domain from Hahella chejuensis. It folds into a typical βγ-crystallin structure upon Ca2+binding and acts as a Ca2+-regulated conformational switch. Besides Hahellin, another two putative βγ-crystallins from Caulobacter crescentus and Yersinia pestis are shown to be partially disordered in their apo-form and undergo large conformational changes upon Ca2+binding, although whether they acquire a βγ-crystallin fold is not known. The extent of conformational disorder/order of a protein is determined by its amino acid sequence. To date how this sequence-structure relationship is reflected in the βγ-crystallin superfamily has not been investigated. In this work, we comparatively studied the sequence and structure of Hahellin with those of Protein S, an ordered βγ-crystallin, via various computational biophysical techniques. We found that several factors, including presence of a C-terminal disorder prone region, high content of energetic frustrations, and low contact density, may promote the formation of the disordered state of apo-Hahellin. We also analyzed the disorder propensities for other putative disordered βγ-crystallin domains. This study provides new clues for further understanding the sequence-structure-function relationship of βγ-crystallins.
authors.affiliation: a Department of Biological Engineering and Institute of Biomedical and Pharmaceutical Sciences , Hubei University of Technology , Wuhan , Hubei 430068 , China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: a Department of Biological Engineering and Institute of Biomedical and Pharmaceutical Sciences , Hubei University of Technology , Wuhan , Hubei 430068 , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: a Department of Biological Engineering and Institute of Biomedical and Pharmaceutical Sciences , Hubei University of Technology , Wuhan , Hubei 430068 , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a Department of Biological Engineering and Institute of Biomedical and Pharmaceutical Sciences , Hubei University of Technology , Wuhan , Hubei 430068 , China.
authors.forename: Zhengding
authors.initials: Z
authors.lastname: Su
authors.affiliation: a Department of Biological Engineering and Institute of Biomedical and Pharmaceutical Sciences , Hubei University of Technology , Wuhan , Hubei 430068 , China.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
chemical_list: D003459:Crystallins; D064267:Intrinsically Disordered Proteins
keywords: crystallin; disorder analysis; energy frustration; intrinsically disordered proteins; sequence–structure relationship