ATP-Bound States of GroEL Captured by Cryo-Electron Microscopy

Ranson, Neil A.; Farr, George W.; Roseman, Alan M.; Gowen, Brent; Fenton, Wayne A.; Horwich, Arthur L.; Saibil, Helen R.

doi:10.1016/s0092-8674(01)00617-1

Cited by 271 publications

(328 citation statements)

References 46 publications

Supporting

Mentioning

313

Contrasting

Order By: Relevance

“…1). During this transition, apical domains move up Ϸ10°and rotate counterclockwise Ϸ25° (33). To ascertain the effect of ATP binding on the SP conformational change we considered three values (see SI Table 1 Distribution functions characterizing the global structural features of the SP at 300 K. (a) Probability distribution P(R g) of the radius of gyration (Rg) of the SP in the bulk.…”

Section: Sp Capture Kinetics Involves Multiple Time Scales and Mechanmentioning

confidence: 99%

Coupling between allosteric transitions in GroEL and assisted folding of a substrate protein

Stan

Lorimer

Thirumalai

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Escherichia coli chaperonin, GroEL, helps proteins fold under nonpermissive conditions. During the reaction cycle, GroEL undergoes allosteric transitions in response to binding of a substrate protein (SP), ATP, and the cochaperonin GroES. Using coarse-grained representations of the GroEL and GroES structures, we explore the link between allosteric transitions and the folding of a model SP, a de novo-designed four-helix bundle protein, with low spontaneous yield. The ensemble of GroEL-bound SP is less structured than the bulk misfolded structures. Upon binding, which kinetically occurs in two stages, the SP loses not only native tertiary contacts but also experiences a decrease in helical content. During multivalent binding and the subsequent ATP-driven transition of GroEL the SP undergoes force-induced stretching. Upon encapsulation, which occurs upon GroES binding, the SP finds itself in a ''hydrophilic'' cavity in which it can reach the folded conformation. Surprisingly, we find that the yield of the native state in the expanded GroEL cavity is relatively small even after it remains in it for twice the spontaneous folding time. Thus, in accord with the iterative annealing mechanism, multiple rounds of binding, partial unfolding, and release of the SP are required to enhance the yield of the folded SP.native state yield ͉ soft nanomachine ͉ force-induced stretching

show abstract

Section: Sp Capture Kinetics Involves Multiple Time Scales and Mechanmentioning

confidence: 99%

Coupling between allosteric transitions in GroEL and assisted folding of a substrate protein

Stan

Lorimer

Thirumalai

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The fluctuating salt-bridge interactions, visible in recently reported EM densities [12], involve residues that are conserved in all GroEL sequences, thus highlighting their functional importance [41]. At the intra-ring level, the R197-E386 salt bridge between the intermediate and the apical domains of two adjacent subunits that is found in the unliganded (apo) state is replaced by K80-E386 in the ATP-bound state [34], whereas E255-K207 switches to E255-K245 in the ATP-bound state (Fig. 3B) [12].…”

Section: Atp Bindingmentioning

confidence: 89%

“…Cryo-EM studies further showed an altered interaction pattern at the inter-ring interface after ATP binding [34,38], which is interpreted as the main mechanism for negative inter-ring cooperativity. Helix D, located in the equatorial domain, couples the ATP binding site of a subunit in one ring to an adjacent subunit of the opposite ring (Fig.…”

Section: Atp Bindingmentioning

confidence: 91%

“…This triggers the first large-scale conformational events in the two-stage transition to the fully extended GroEL/ES structure, whereas there are only minor changes in the opposite, folding inactive ring (denoted trans) [38]. This first step entails concerted movements of individual domains in the cis ring to produce an intermediate, semi-relaxed (R1) state that is slightly expanded compared to the unliganded, tense (T) state [12,34,38]. That these motions must be concerted was first appreciated by early computational studies, which showed that non-concerted motions would impede transition due to steric intra-ring clashes [39,40].…”

Section: Atp Bindingmentioning

confidence: 99%

See 1 more Smart Citation

Dynamics, flexibility, and allostery in molecular chaperonins

et al. 2015

View full text Add to dashboard Cite

a b s t r a c tThe chaperonins are a family of molecular chaperones present in all three kingdoms of life. They are classified into Group I and Group II. Group I consists of the bacterial variants (GroEL) and the eukaryotic ones from mitochondria and chloroplasts (Hsp60), while Group II consists of the archaeal (thermosomes) and eukaryotic cytosolic variants (CCT or TRiC). Both groups assemble into a dual ring structure, with each ring providing a protective folding chamber for nascent and denatured proteins. Their functional cycle is powered by ATP binding and hydrolysis, which drives a series of structural rearrangements that enable encapsulation and subsequent release of the substrate protein.Chaperonins have elaborate allosteric mechanisms to regulate their functional cycle. Long-range negative cooperativity between the two rings ensures alternation of the folding chambers. Positive intra-ring cooperativity, which facilitates concerted conformational transitions within the protein subunits of one ring, has only been demonstrated for Group I chaperonins. In this review, we describe our present understanding of the underlying mechanisms and the structurefunction relationships in these complex protein systems with a particular focus on the structural dynamics, allostery, and associated conformational rearrangements.

show abstract

“…Leu 400 and Arg 404 in the T state (Protein Data Bank code 1OEL) (31), R state (code 2C7E) (32), and RЉ state (code 1AON) (1) of EC GroEL are shown in Fig. 5.…”

Section: Groel1 From C Pneumoniae Acts As a Chaperonin-mentioning

confidence: 99%

The Intermediate Domain Defines Broad Nucleotide Selectivity for Protein Folding in Chlamydophila GroEL1

Okuda

Sakuhana

Yamamoto

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

The chaperonin GroEL assists protein folding in the presence of ATP and magnesium through substrate protein capsulation in combination with the cofactor GroES. Recent studies have revealed the details of folding cycles of GroEL from Escherichia coli, yet little is known about the GroEL-assisted protein folding mechanisms in other bacterial species. Using three model enzyme assays, we have found that GroEL1 from Chlamydophila pneumoniae, an obligate human pathogen, has a broader selectivity for nucleotides in the refolding reaction. To elucidate structural factors involved in such nucleotide selectivity, GroEL chimeras were constructed by exchanging apical, intermediate, and equatorial domains between E. coli GroEL and C. pneumoniae GroEL1. In vitro folding assays using chimeras revealed that the intermediate domain is the major contributor to the nucleotide selectivity of C. pneumoniae GroEL1. Additional site-directed mutation experiments led to the identification of Gln 400 and Ile 404 in the intermediate domain of C. pneumoniae GroEL1 as residues that play a key role in defining the nucleotide selectivity of the protein refolding reaction.

show abstract

ATP-Bound States of GroEL Captured by Cryo-Electron Microscopy

Cited by 271 publications

References 46 publications

Coupling between allosteric transitions in GroEL and assisted folding of a substrate protein

Coupling between allosteric transitions in GroEL and assisted folding of a substrate protein

Dynamics, flexibility, and allostery in molecular chaperonins

The Intermediate Domain Defines Broad Nucleotide Selectivity for Protein Folding in Chlamydophila GroEL1

Contact Info

Product

Resources

About