Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BioTecMed), Departament de Bioquímica i Biologia Molecular, Universitat de València, E-46100, Burjassot, Spain.
School of Physics, School of Chemistry and Biochemistry, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
Nat Commun. 2018 Dec 7;9(1):5246. doi: 10.1038/s41467-018-07554-7.
Integral membrane proteins are assembled into the ER membrane via a continuous ribosome-translocon channel. The hydrophobicity and thickness of the core of the membrane bilayer leads to the expectation that transmembrane (TM) segments minimize the cost of harbouring polar polypeptide backbones by adopting a regular pattern of hydrogen bonds to form α-helices before integration. Co-translational folding of nascent chains into an α-helical conformation in the ribosomal tunnel has been demonstrated previously, but the features governing this folding are not well understood. In particular, little is known about what features influence the propensity to acquire α-helical structure in the ribosome. Using in vitro translation of truncated nascent chains trapped within the ribosome tunnel and molecular dynamics simulations, we show that folding in the ribosome is attained for TM helices but not for soluble helices, presumably facilitating SRP (signal recognition particle) recognition and/or a favourable conformation for membrane integration upon translocon entry.
整合膜蛋白通过连续的核糖体-移位子通道组装到内质网膜中。膜双层核心的疏水性和厚度使得人们期望跨膜（TM）片段通过采用氢键的规则模式形成α-螺旋来最小化容纳极性多肽骨架的成本，然后再进行整合。先前已经证明了新生链在核糖体隧道中以α-螺旋构象共翻译折叠，但控制这种折叠的特征尚不清楚。特别是，关于哪些特征会影响核糖体中获得α-螺旋结构的倾向知之甚少。通过在核糖体隧道内捕获的截断新生链的体外翻译和分子动力学模拟，我们表明折叠发生在 TM 螺旋中，但不在可溶性螺旋中，这可能有助于 SRP（信号识别颗粒）识别和/或有利于易位进入时的膜整合构象。
