title: The GPI anchor signal sequence dictates the folding and functionality of the Als5 adhesin from Candida albicans.
abstract: BACKGROUND
  Proteins destined to be Glycosylphosphatidylinositol (GPI) anchored are translocated into the ER lumen completely before the C-terminal GPI anchor attachment signal sequence (SS) is removed by the GPI-transamidase and replaced by a pre-formed GPI anchor precursor. Does the SS have a role in dictating the conformation and function of the protein as well?
  
  
  RESULTS
  We generated two variants of the Als5 protein without and with the SS in order to address the above question. Using a combination of biochemical and biophysical techniques, we show that in the case of Als5, an adhesin of C. albicans, the C-terminal deletion of 20 amino acids (SS) results in a significant alteration in conformation and function of the mature protein.
  
  
  CONCLUSIONS
  We propose that the locking of the conformation of the precursor protein in an alternate conformation from that of the mature protein is one probable strategy employed by the cell to control the behaviour and function of proteins intended to be GPI anchored during their transit through the ER.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Mohammad Faiz
authors.initials: MF
authors.lastname: Ahmad
authors.forename: Bhawna
authors.initials: B
authors.lastname: Yadav
authors.forename: Pravin
authors.initials: P
authors.lastname: Kumar
authors.forename: Amrita
authors.initials: A
authors.lastname: Puri
authors.forename: Mohit
authors.initials: M
authors.lastname: Mazumder
authors.forename: Anwar
authors.initials: A
authors.lastname: Ali
authors.forename: Samudrala
authors.initials: S
authors.lastname: Gourinath
authors.forename: Rohini
authors.initials: R
authors.lastname: Muthuswami
authors.forename: Sneha Sudha
authors.initials: SS
authors.lastname: Komath
mesh_terms: D019943:Amino Acid Substitution; D002176:Candida albicans; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D024141:Collagen Type IV / Q000737:chemistry / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D021382:Protein Sorting Signals / Q000235:genetics*; D017433:Protein Structure, Secondary / Q000235:genetics
chemical_list: C109455:ALA1 protein, Candida albicans; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D005656:Fungal Proteins; D017261:Glycosylphosphatidylinositols; D021382:Protein Sorting Signals