Structural mimicry of proline kinks: tertiary packing interactions support local structural distortions. Academic Article uri icon

Overview

abstract

  • Proline residues in the helical segments of soluble and transmembrane proteins have received special attention from both a structural and functional perspective. A feature of these helices is the structural distortion termed "proline-kink", which has been associated with the presence of the proline residue. However, a recent report on the yeast heat-shock transcription factor of Kluyveromyces lactis (HSF_KL) suggests that these proline-associated deformations can be achieved in the absence of proline residues, thus raising the question of the mechanisms responsible for the structural mimicry of proline-related features. In this study, the specific interactions responsible for the distortion were characterized by comparative analysis of the atomic details of the packing interactions that surround the evolutionarily conserved proline-kink in the alpha2 helix of HSF_KL and a set of 39 structurally related proteins that lacked the distortion. The mechanistic details inferred from this analysis were confirmed with molecular dynamics simulations. The study shows that the packing interactions between the alpha2 and alpha1 helices in HSF_KL are responsible for the stabilization of the conserved kink, whether a proline residue that divides the helix into segments is present or not. The proline-kink can facilitate the formation of tertiary packing interactions that would otherwise not be possible. However, it is the ability to establish differential packing interactions for the helix segments, rather than the structural properties of the proline-kink itself, that emerges as the key factor for the characteristic distortion.

publication date

  • May 17, 2002

Research

keywords

  • DNA-Binding Proteins
  • Heat-Shock Proteins
  • Proline
  • Protein Folding
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors

Identity

Scopus Document Identifier

  • 0036314934

Digital Object Identifier (DOI)

  • 10.1016/s0022-2836(02)00221-8

PubMed ID

  • 12083514

Additional Document Info

volume

  • 318

issue

  • 5