An elongated spine of buried core residues necessary for in vivo folding of the parallel beta-helix of P22 tailspike adhesin.

Proceedings of the National Academy of Sciences of the United States of America
Ryan Simkovsky, J King

Abstract

The parallel beta-helix is an elongated beta-sheet protein domain associated with microbial virulence factors, toxins, viral adhesins, and allergens. Long stacks of similar, buried residues are a prominent feature of this fold, as well as the polypeptide chain fold of an amyloid structure. The 13-rung, right-handed, parallel beta-helix of the homotrimeric P22 tailspike adhesin exhibits predominantly hydrophobic stacks. The role of these stacked residues in the folding and stabilization of the protein is unclear. Through scanning alanine mutagenesis we have identified a folding spine of stacked residues in continuous contact along the length of P22 tailspike's beta-helix domain that is necessary for folding within cells. Nearly all chains carrying alanine substitutions of the 103 buried nonalanines were defective in folding in vivo at 37 degrees C. However, the majority of these chains successfully reached a native state, stable to >80 degrees C, when folded inside cells at low temperatures. Thus, nearly the entire buried core was critical for in vivo beta-helix folding but negligible for stability. Folding at 18 degrees C revealed the minimal folding spine of 29 nonglycine stack positions that were intolerant to alanine substit...Continue Reading

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Citations

Jul 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Matthew L BakerWah Chiu
Sep 18, 2009·The Journal of Biological Chemistry·Kate L Moreau, Jonathan King
Mar 17, 2011·PloS One·Melissa C GarciaPeter N Lipke
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Mar 25, 2011·Protein Science : a Publication of the Protein Society·Fanrong Kong, Jonathan King
Oct 23, 2009·Proteins·Mirco Junker, Patricia L Clark
Aug 5, 2008·Journal of Molecular Biology·Michael S EvansPatricia L Clark
Dec 7, 2013·Journal of Virology·Desislava A RaytchevaJonathan A King
Jan 4, 2019·Soft Matter·Elizabeth P DeBenedictis, Sinan Keten
Jun 6, 2006·Protein Science : a Publication of the Protein Society·Junghwa Kim, Anne Skaja Robinson
Jun 22, 2010·Biopolymers·Atanu Das, Chaitali Mukhopadhyay
Dec 29, 2006·The Journal of Biological Chemistry·Woo-Suk JungSangkee Rhee
Oct 30, 2013·The Journal of Biological Chemistry·Wanyoike Kang'ethe, Harris D Bernstein
Feb 2, 2020·The Journal of Biological Chemistry·Nischay K RegeMichael A Weiss
Apr 14, 2015·IUCrJ·Guillaume A SchochMarkus G Rudolph
Mar 18, 2009·Biochemistry·Céline GalvagnionElizabeth M Meiering

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