Contributions to the Field of Intracellular Protein Trafficking
Following is a partial timelline of Günter
Blobel's original, groundbreaking accomplishments:
Proposed, with David Sabatini, that information for
translocation of secretory proteins across the endoplasmic reticulum
membrane resides in the NH2 terminal sequence.
Developed the first cell-free system that faithfully
reproduces protein translocation. This system became the paradigm
for all other subsequently developed cell-free translocation systems
(bacteria, mitochondria, chloroplasts, peroxisomes). More importantly,
it provided the opportunity for extensive biochemical analysis of
Expanded and shaped the proposal he and Sabatini made
in 1971 into the "signal hypothesis."
Determined the partial primary structure of signal
sequences of several presecretory proteins by Edman degradation.
First demonstrated that a nucleus-encoded, cytosol-synthesized
protein of the chloroplast stroma is synthesized as a precursor,
consistent with the idea that it contains a transient, chloroplast-targeted
Provided the first example of an integral membrane
protein shown to contain an NH2 termnal sequence
extension that is the structural and functional equivalent of the
signal sequence of presecretory proteins.
Established for the first time a cell-free protein
translocation system that mimicked the integration of a bacterial
integral membrane protein into the bacterial plasma membrane. First
demonstrated a membrane-associated bacterial signal peptidase.
First demonstrated that nucleus-encoded, cystosol-synthesized
mitochondrial matrix proteins are synthesized as larger precursors,
and developed the first cell-free system that mimics protein import
First achieved the cell-free synthesis of a precursor
for a lysosomal protein and translocation into microsomal vesicles.
Elucidated, by Edman degradation, the primary structure
of the first chloroplast stroma-targeted signal sequence.
Extended the signal hypothesis to a general hypothesis
on intracellular protein traffic and membrane biogenesis, and proposed
the concept of "topogenic" sequences.
First isolated component-catalyzing, signal sequence-mediated
translocation across the ER.
Showed that the isolated protein specifically recognizes
signal sequences of nascent presecretory proteins, and named it
the "signal recognition protein," or SRP. Postulated the
existence of an "SRP receptor" in the microsomal membrane.
Elucidated the primary structure of the first signal
sequence for a lysosomal protein.
Showed that SRP contains a 7S RNA molecule in the
stoichiometry of one 7S RNA and one each of six different proteins.
The term SRP now stands for "signal recognition particle."
Purified the predicted SRP receptor from microsomal
Elucidated the first primary structure for a signal
sequence that targets proteins to mitochondria, this time by cDNA
cloning rather than by Edman degradation.
Demonstrated that the SRP receptor functions in targeting
by releasing the signal sequence from SRP, and SRP from the ribosome.
Purified the ER-associated signal peptidase as a complex
of five polypeptide chains.
Identified a "signal sequence receptor"
for protein import into chloroplasts.
First isolated a specific signal recognition factor
that binds to signal sequences of bacterial presecretory protein.
Completely solubilized ribosome-stripped and salt-extracted
microsomal membranes by detergents. Removal of the detergents yielded
reconstituted vesicles that are fully translocation-competent. This
result was a crucial condition for the biochemical analyses of membrane
proteins required for translocation, such as the SRP receptor, the
protein conducting channel and other yet-to-be-identified membrane
Identified a mitochondrial "signal sequence receptor"
for protein import into yeast mitochondria.
Cloned and sequenced the cDNA for the import receptor
Demonstrated the existence of a protein-conducting
channel in the ER by electrophysiological procedures.
Demonstrated that signal peptides are sufficient for
opening the protein-conducting channels.
Identified the requirement for the ATP binding protein
RAN in nuclear transport.
Identified the protein translocation machinery of
Showed that p10, a protein with a previously unknown
function, plays a major role in the import of proteins into the
Observed the protein-conducting channels bound to
ribosomes using cryo-electron microscopy Identified the pathway
used to import ribosome proteins into the nucleus.
Determined the crystal structures of the nuclear
transport factors karyopherin alpha and beta.