Signal sequences control gating of the protein translocation channel in a substrate-specific manner.
N-terminal signal sequences mediate targeting of nascent chains to the endoplasmic reticulum and facilitate opening of the protein translocation channel to the passage of substrate. We have assessed each of these steps for a diverse set of mammalian signals. While minimal differences were seen in their targeting function, signal sequences displayed a remarkable degree of variation in initiating nascent chain access to the lumenal environment. Such substrate-specific properties of signals were evolutionarily conserved, functionally matched to their respective mature domains, and important for the proper biogenesis of some proteins. Thus, the sequence variations of signals do not simply represent functional degeneracy, but instead encode critical differences in translocon gating that are coordinated with their respective passengers to facilitate efficient translocation.
Kim
Soo Jung
SJ
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892, USA.
Mitra
Devarati
D
Salerno
Jeffrey R
JR
Hegde
Ramanujan S
RS
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017124:Conserved Sequence; D019143:Evolution, Molecular; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity
D026901:Membrane Transport Proteins; D021382:Protein Sorting Signals; D011506:Proteins